43 results on '"Rocha, João"'
Search Results
2. The Thiol-Modifier Effects of Organoselenium Compounds and Their Cytoprotective Actions in Neuronal Cells
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Galant, Letícia Selinger, Rafique, Jamal, Braga, Antônio Luiz, Braga, Felipe Camargo, Saba, Sumbal, Radi, Rafael, da Rocha, João Batista Teixeira, Santi, Claudio, Monsalve, Maria, Farina, Marcelo, and de Bem, Andreza Fabro
- Published
- 2021
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3. Quality Studies on Cynometra iripa Leaf and Bark as Herbal Medicines.
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Sabiha, Shabnam, Hasan, Kamrul, Lima, Katelene, Malmir, Maryam, Serrano, Rita, Moreira da Silva, Isabel, Rocha, João, Islam, Nurul, and Silva, Olga
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HERBAL medicine ,PHYTOCHEMICALS ,CALCIUM oxalate ,AYURVEDIC medicine ,VITAMIN C ,PROANTHOCYANIDINS - Abstract
Cynometra iripa Kostel. is a Fabaceae species of mangrove used in traditional Ayurvedic medicine for treating inflammatory conditions. The present study aims to establish monographic botanical and chemical quality criteria for C. iripa leaf and bark as herbal substances and to evaluate their in vitro antioxidant potential. Macroscopic and microscopic qualitative and quantitative analyses, chemical LC-UV/DAD-ESI/MS profiling, and the quantification of key chemical classes were performed. Antioxidant activity was evaluated by DPPH and FRAP assays. Macroscopically, the leaf is asymmetrical with an emarginated apex and cuneate base. Microscopically, it shows features such as two-layered adaxial palisade parenchyma, vascular bundles surrounded by 3–6 layers of sclerenchyma, prismatic calcium oxalate crystals (5.89 ± 1.32 μm) along the fibers, paracytic stomata only on the abaxial epidermis (stomatal index–20.15), and non-glandular trichomes only on petiolules. The microscopic features of the bark include a broad cortex with large lignified sclereids, prismatic calcium oxalate crystals (8.24 ± 1.57 μm), and secondary phloem with distinct 2–5 seriated medullary rays without crystals. Chemical profile analysis revealed that phenolic derivatives, mainly condensed tannins and flavonoids, are the main classes identified. A total of 22 marker compounds were tentatively identified in both plant parts. The major compounds identified in the leaf were quercetin-3-O-glucoside and taxifolin pentoside and in the bark were B-type dimeric proanthocyanidins and taxifolin 3-O-rhamnoside. The total phenolics content was higher in the leaf (1521 ± 4.71 mg GAE/g dry weight), while the total flavonoids and condensed tannins content were higher in the bark (82 ± 0.58 mg CE/g and 1021 ± 5.51 mg CCE/g dry weight, respectively). A total of 70% of the hydroethanolic extracts of leaf and bark showed higher antioxidant activity than the ascorbic acid and concentration-dependent scavenging activity in the DPPH assay (IC
50 23.95 ± 0.93 and 23.63 ± 1.37 µg/mL, respectively). A positive and statistically significant (p < 0.05) correlation between the phenol content and antioxidant activity was found. The results obtained will provide important clues for the quality control criteria of C. iripa leaf and bark, as well as for the knowledge of their pharmacological potential as possible anti-inflammatory agents with antioxidant activity. [ABSTRACT FROM AUTHOR]- Published
- 2024
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4. The Biochemical, Microbiological, Antioxidant and Sensory Characterization of Fermented Skimmed Milk Drinks Supplemented with Probiotics Lacticaseibacillus casei and Lacticaseibacillus rhamnosus.
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Shabbir, Iqra, Al-Asmari, Fahad, Saima, Hafiza, Nadeem, Muhammad Tahir, Ambreen, Saadia, Kasankala, Ladislaus Manaku, Khalid, Muhammad Zubair, Rahim, Muhammad Abdul, Özogul, Fatih, Bartkiene, Elena, and Rocha, João Miguel
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SKIM milk ,FERMENTED milk ,FERMENTED foods ,LACTIC acid bacteria ,PROBIOTICS ,DAIRY products - Abstract
A variety of foods fermented with lactic acid bacteria (LAB) serve as dietary staples in many countries. The incorporation of health-promoting probiotics into fermented milk products can have profound effects on human health. Considering the health benefits of Yakult, the current study was undertaken to develop an enriched Yakult-like fermented skimmed milk drink by the addition of two probiotic strains, namely Lacticaseibacillus casei (Lc) and Lacticaseibacillus rhamnosus (Lr). The prepared drinks were compared in terms of various parameters, including their physicochemical properties, proximate chemical composition, mineral estimation, microbial viable count, antioxidant activity, and sensory evaluation. Each strain was employed at five different concentrations, including 1% (T
1 ), 1.5% (T2 ), 2% (T3 ), 2.5% (T4 ), and 3% (T5 ). The prepared Yakult samples were stored at 4 °C and analyzed on days 0, 7, 14, 21, and 28 to evaluate biochemical changes. The findings revealed that the concentration of the starter culture had a significant (p ≤ 0.05) impact on the pH value and moisture and protein contents, but had no marked impact on the fat or ash content of the developed product. With the Lc strain, Yakult's moisture content ranged from 84.25 ± 0.09 to 85.65 ± 0.13%, whereas with the Lr strain, it was from 84.24 ± 0.08 to 88.75 ± 0.13%. Protein levels reached their highest values with T5 (3% concentration). The acidity of all treatments increased significantly due to fermentation and, subsequently, pH showed a downward trend (p ≤ 0.05). The total soluble solids (TSS) content decreased during storage with Lc as compared to Lr, but the presence of carbohydrates had no appreciable impact. The drink with Lc exhibited a more uniform texture and smaller pore size than Yakult with Lr. Except for the iron values, which showed an increasing trend, the contents of other minerals decreased in increasing order of the added probiotic concentration used: 1% (T1 ), 1.5% (T2 ), 2% (T3 ), 2.5% (T4 ), and 3% (T5 ). The highest lactobacilli viable count of 8.69 ± 0.43 colony-forming units (CFU)/mL was observed with the T1 Lr-containing drink at the end of the storage period. Regarding the storage stability of the drink, the highest value for DPPH (88.75 ± 0.13%) was found with the T1 Lc drink on day 15, while the highest values for FRAP (4.86 ± 2.80 mmol Fe2+ /L), TPC (5.97 ± 0.29 mgGAE /mL), and TFC (3.59 ± 0.17 mgGAE /mL) were found with the T5 Lr drink on day 28 of storage. However, the maximum value for ABTS (3.59 ± 0.17%) was noted with the T5 Lr drink on the first day of storage. The results of this study prove that Lc and Lr can be used in dairy-based fermented products and stored at refrigerated temperatures. [ABSTRACT FROM AUTHOR]- Published
- 2023
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5. Catuaba (Trichilia catigua) Prevents Against Oxidative Damage Induced by In Vitro Ischemia–Reperfusion in Rat Hippocampal Slices
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Kamdem, Jean Paul, Waczuk, Emily Pansera, Kade, Ige Joseph, Wagner, Caroline, Boligon, Aline Augusti, Athayde, Margareth Linde, Souza, Diogo Onofre, and Rocha, João Batista Teixeira
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- 2012
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6. Antioxidant activity and low toxicity of (E)-1-(1-(methylthio)-1-(selenopheny) hept-1-en-2-yl) pyrrolidin-2-one
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Ineu, Rafael Porto, dos Santos, Matheus, do Rêgo Barros, Olga Soares, Nogueira, Cristina Wayne, Rocha, João Batista Teixeira, Zeni, Gilson, and Pereira, Maria Ester
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- 2012
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7. Evaluation of the biological effects of (S)-dimethyl 2-(3-(phenyltellanyl) propanamido) succinate, a new telluroamino acid derivative of aspartic acid
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Meinerz, Daiane Francine, Sudati, Jéssie H., dos Santos, Danúbia B., Frediani, Andressa, Alberto, Eduardo E., Allebrandt, Josiane, Franco, Jeferson L., Barbosa, Nilda B. V., Aschner, Michael, and da Rocha, João Batista T.
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- 2011
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8. Antioxidant properties of oxime 3-(phenylhydrazono) butan-2-one
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Puntel, Gustavo Orione, Gubert, Priscila, Peres, Gisele Louro, Bresolin, Leandro, Rocha, João Batista Teixeira, Pereira, Maria Ester, Carratu, Vanessa Santana, and Soares, Félix A. Antunes
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- 2008
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9. Krebs Cycle Intermediates Modulate Thiobarbituric Acid Reactive Species (TBARS) Production in Rat Brain In Vitro
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Puntel, Robson L., Nogueira, Cristina W., and Rocha, João B. T.
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- 2005
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10. Anti-inflammatory Effects of Persimmon (Diospyros kaki L.) in Experimental Rodent Rheumatoid Arthritis.
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Direito, Rosa, Rocha, João, Serra, Ana-Teresa, Fernandes, Adelaide, Freitas, Marisa, Fernandes, Eduarda, Pinto, Rui, Bronze, Rosário, Sepodes, Bruno, and Figueira, Maria-Eduardo
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ANIMAL experimentation , *ANTI-inflammatory agents , *BIOLOGICAL models , *COLLAGEN , *FRUIT , *HISTOLOGY , *RADIOGRAPHY , *RHEUMATOID arthritis , *RODENTS , *TRADITIONAL medicine , *PLANT extracts , *TREATMENT effectiveness , *DISEASE incidence , *PHARMACODYNAMICS - Abstract
Persimmon (Diospyros kaki L.) fruits are used in traditional medicine largely due to their claimed beneficial effects on human health. The aim of this work was to evaluate the anti-inflammatory activity of a persimmon extract in rats with collagen-induced arthritis (CIA). CIA was induced in Wistar rats through an intradermal injection of an emulsion of bovine type II collagen (CII) in complete Freund's adjuvant (FCA). Macroscopic evidence of CIA first appeared as periarticular erythema and edema in the hind paws. The incidence of CIA was 100% by day 27 in the CII-challenged rats, and the severity of CIA progressed for 35 days. Radiographs revealed focal resorption of bone, with osteophyte formation in the tibiotarsal joint and soft tissue swelling. The histopathologic features included erosion of the cartilage at the joint margins. The persimmon extract showed an anti-inflammatory effect given the significant reduction in both the edema volume and radiological alterations attributed to CIA in the bone. We demonstrate that the administration of persimmon extract attenuates the degree of chronic inflammation and tissue damage characteristic of CIA in rats, most probably by the potent antioxidant characteristics of the extract. [ABSTRACT FROM AUTHOR]
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- 2020
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11. In silico evidences of Mpro inhibition by a series of organochalcogen-AZT derivatives and their safety in Caenorhabditis elegans.
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Viçozzi, Gabriel Pedroso, de Oliveira Pereira, Flávia Suelen, da Silva, Rafael Santos, Leal, Julliano Guerin, Sarturi, Joelma Menegazzi., Nogara, Pablo Andrei, Rodrigues, Oscar Endrigo Dorneles, Teixeira da Rocha, João Batista, and Ávila, Daiana Silva
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SARS-CoV-2 ,CAENORHABDITIS elegans ,CELL nuclei ,HIV infections ,SULFHYDRYL group ,ANTIVIRAL agents - Abstract
The new coronavirus (SARS-CoV-2) pandemic emerged in 2019 causing millions of deaths. Vaccines were quickly developed and made available in 2021. Despite the availability of vaccines, some subjects refuse to take the immunizing or present comorbities, therefore developing serious cases of COVID-19, which makes necessary the development of antiviral drugs. Previous studies have demonstrated that ebselen, a selenium-containing molecule, can inhibit SARS-CoV-2 Mpro. In addition, selenium is a trace element that has antiviral and anti-inflammatory properties. Zidovudine (AZT) has been widely used against HIV infections and its action against SARS-CoV-2 may be altered by the structural modification with organochalcogen moieties, but this hypothesis still needs to be tested. In the present work we evaluated the Mpro inhibition capacity (in silico), the safety and antioxidant effect of six organochalcogen AZT-derivatives using the free-living nematode Caenorhabditis elegans , through acute (30 min) and chronic (48) exposure protocols. We observed that the molecules were safe at a concentration range of 1–500 µM and did not alter any toxicological endpoint evaluated. Furthermore, the molecules are capable to decrease the ROS formation stimulated by hydrogen peroxide, to modulate the expression of important antioxidant enzymes such superoxide-dismutase-3 and glutathione S-transferese-4 and to stimulate the translocation of the DAF-16 to the cell nucleus. In addition, the molecules did not deplete thiol groups, which reinforces their safety and contribution to oxidative stress resistance. We have found that compounds S116l (a Tellurium AZT-derivative) and S116h (a Selenium-AZT derivative) presented more promising effects both in silico and in vivo , being strong candidates for further in vivo studies. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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12. Phytochemical constituents and in vitro antioxidant capacity of Tabernaemontana catharinensis A. DC.
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Boligon, Aline Augusti, de Freitas, Robson Borba, de Brum, Thiele Faccim, Piana, Mariana, Vargas Belke, Bianca, Teixeira da Rocha, João Batista, and Athayde, Margareth Linde
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TABERNAEMONTANA ,DNA damage ,PLANT extracts - Abstract
Introduction: Free radicals induce numerous diseases by lipid peroxidation, protein peroxidation, and DNA damage. It has been reported that numerous plant extracts have antioxidant activities to scavenge free radicals. In this present study we determined the in vitro antioxidant capacity and quantified of total phenolics, flavonoids, tannins and alkaloids of Tabernaemontana catharinensis crude extract and fractions leaves. Methods: The antioxidant potential was evaluated by 1,1-diphenyl-2-picryl-hydrazyl free radical (DPPH) scavenging and thiobarbituric acid reactive species (TBARS) methods, total phenolics content was determined using the FolineCiocalteu assay, flavonoids, tannins and alkaloids were determined by spectrophotometer. Results: Crude extract and fractions showed inhibition against TBARS, ethyl acetate was the most effective fraction (IC
50 ± 6.71 ± 0.19 µg/mL), subsequently by butanolic (26.15 ± 0.08 µg/mL), dichloromethane (43.25 ± 0.12 mg/mL) and crude extract (61.09 ± 0.05 mg/mL), respectively. Moreover, the DPPH assay, presented IC50 value ranged of 4.64 ± 1.25 to 27.78 ± 0.93 µg/mL. Contents of total phenols, flavonoids, tannins and alkaloids of T. catharinensis followed the order: ethyl acetate > butanolic > dichloromethane fractions > crude extract. Conclusion: The present study, we found that the crude extract and fractions of T. catharinensis showed good antioxidant activity. Among the samples tested, the ethyl acetate fraction showed better activity than others. [ABSTRACT FROM AUTHOR]- Published
- 2013
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13. Phytochemical characterization and in vitro antioxidant properties of Lantana camara L. and Lantana montevidensis Briq
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Sousa, Erlânio O., Rocha, João B.T., Barros, Luiz M., Barros, Adriana R.C., and Costa, José G.M.
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PHYTOCHEMICALS , *ANTIOXIDANTS , *LANTANA camara , *BIOACTIVE compounds , *PLANT products , *FLAVONOIDS - Abstract
Abstract: There is a growing interest of industry to replace synthetic chemicals by natural products with bioactive properties from plant origin. The aim of the present study was the phytochemical characterization and in vitro antioxidant of Lantana camara L. e Lantana montevidensis Briq. The bicyclogermacrene (19.42%), isocaryophyllene (16.70%), valencene (12.94%) and germacrene D (12.34%) were the main constituents of the oil from L. camara, while in the oil from L. montevidensis were β-caryophyllene (31.50%), germacrene D (27.50%) and bicyclogermacrene (13.93%). Phenolic compounds were identified; flavonoids (quercetin and rutin) and phenolic acids (gallic, chlorogenic and caffeic acids) were quantified by HPLC-DAD. Free radical scavenger properties of essential oils and ethanolic extracts were assessed by 1,1-diphenyl-2-picrylhydrazyl (DPPH). Essential oils and extracts promoted an inhibition of the radical DPPH. The extracts of the leaves exhibit lowest IC50 values, indicating the highest potential as free radical scavengers. Our research indicates that those plants good potential in scavenging free radicals and can be an important source of antioxidant phytochemical. [Copyright &y& Elsevier]
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- 2013
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14. Acute exposure of rabbits to diphenyl diselenide: a toxicological evaluation.
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Straliotto, Marcos Raniel, Mancini, Gianni, de Oliveira, Jade, Nazari, Evelise Maria, Müller, Yara Maria Rauh, Dafre, Alcir, Ortiz, Susana, Silva, Edson Luiz, Farina, Marcelo, Latini, Alexandra, Rocha, João Batista Teixeira, and de Bem, Andreza Fabro
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BIPHENYL compounds ,TOXICOLOGY ,RABBIT physiology ,LABORATORY rabbits - Abstract
The article presents a study which aims to assess the impact of organoselenium compound diphenyl diselenide (PhSe)
2 's acute administration on toxicological factors in rabbits. The study exposed the adult rabbits from New Zealand to (PhSe)2 one time daily within five days. The results suggests that rabbit's (PhSe)2 acute toxicology is dose-dependent, which should incite other experiments regarding the therapeutic properties of (PhSe)2 .- Published
- 2010
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15. From Diospyros kaki L. (Persimmon) Phytochemical Profile and Health Impact to New Product Perspectives and Waste Valorization.
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Direito, Rosa, Rocha, João, Sepodes, Bruno, and Eduardo-Figueira, Maria
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Persimmon (Diospyros kaki L.) fruit's phytochemical profile includes carotenoids, proanthocyanidins, and gallic acid among other phenolic compounds and vitamins. A huge antioxidant potential is present given this richness in antioxidant compounds. These bioactive compounds impact on health benefits. The intersection of nutrition and sustainability, the key idea behind the EAT-Lancet Commission, which could improve human health and decrease the global impact of food-related health conditions such as cancer, heart disease, diabetes, and obesity, bring the discussion regarding persimmon beyond the health effects from its consumption, but also on the valorization of a very perishable food that spoils quickly. A broad option of edible products with better storage stability or solutions that apply persimmon and its byproducts in the reinvention of old products or even creating new products, or with new and better packaging for the preservation of food products with postharvest technologies to preserve and extend the shelf-life of persimmon food products. Facing a global food crisis and the climate emergency, new and better day-to-day solutions are needed right now. Therefore, the use of persimmon waste has also been discussed as a good solution to produce biofuel, eco-friendly alternative reductants for fabric dyes, green plant growth regulator, biodegradable and edible films for vegetable packaging, antimicrobial activity against foodborne methicillin-resistant Staphylococcus aureus found in retail pork, anti-Helicobacter pylori agents from pedicel extracts, and persimmon pectin-based emulsifiers to prevent lipid peroxidation, among other solutions presented in the revised literature. It has become clear that the uses for persimmon go far beyond the kitchen table and the health impact consumption demonstrated over the years. The desired sustainable transition is already in progress, however, mechanistic studies and clinical trials are essential and scaling-up is fundamental to the future. [ABSTRACT FROM AUTHOR]
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- 2021
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16. Overview of Sourdough Microbiota
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Ceresino, Elaine Berger, Ciont (Nagy), Călina, Pop, Oana Lelia, Ceresino, Elaine Berger, editor, Juodeikiene, Grazina, editor, Miescher Schwenninger, Susanne, editor, and Ferreira da Rocha, João Miguel, editor
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- 2024
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17. Phytosomes with Persimmon (Diospyros kaki L.) Extract: Preparation and Preliminary Demonstration of In Vivo Tolerability.
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Direito, Rosa, Reis, Catarina, Roque, Luís, Gonçalves, Margarida, Sanches-Silva, Ana, Gaspar, Maria Manuela, Pinto, Rui, Rocha, João, Sepodes, Bruno, Rosário Bronze, Maria, and Eduardo Figueira, Maria
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PERSIMMON ,DIOSPYROS ,MONODISPERSE colloids ,BIOLOGICAL membranes ,DIETARY supplements ,SURFACE charges - Abstract
Persimmon (Diospyros kaki L.), a fruit rich in phenolic compounds (PCs), has been considered effective in mitigating oxidative damage induced by an excess of reactive oxygen species. Due to large molecular weight and intrinsic instability in some physiological fluids, PCs' passage through biological membranes is very limited. Carriers like phytosomes are promising systems to optimize oral absorption of encapsulated extracts. This work prepared and fully characterized phytosomes containing bioactive phenolic extracts from persimmon in terms of size, surface charge, encapsulation efficiency and stability over six months. These phytosomes were orally dosed to Wistar rats during a 15-day period. Afterwards, haematological and biochemical analyses were performed. Monodisperse phytosomes were successfully prepared, with size less than 300nm (PI < 0.3) and high encapsulation efficiency (97.4%) of PCs. In contrast to free extract, extract-loaded phytosomes had higher antioxidant activity after 6 months storage. Oral administration of extract-loaded phytosomes and free extract did not lead to lipidic profile changes and were within referenced normal ranges, as well as glycaemia levels and urine parameters. The results highlighted the potential of persimmon PCs as food supplements or pharmacological tools, suggesting a promising and safe phytosomal formulation containing bioactive agents of persimmon that could lead to health benefits. [ABSTRACT FROM AUTHOR]
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- 2019
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18. Effects of diphenyl diselenide on oxidative stress induced by sepsis in rats
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Prauchner, Carlos A., Prestes, Alessandro de S., and da Rocha, João B.T.
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BIPHENYL compounds , *OXIDATIVE stress , *SEPSIS , *LABORATORY rats , *HYPOTHESIS , *BIOLOGICAL assay - Abstract
Abstract: Sepsis is a potentially deadly complication that can be caused by different factors. Actually, it is known that oxidative stress is involved in the pathogenesis of sepsis. Thus, the aim of this study was to evaluate the effect of diphenyl diselenide (PhSe)2, an emergent compound, on oxidative stress parameters induced by sepsis in rats. Animals were pre-injected with (PhSe)2 or vehicle. Twenty-four hours later, sepsis was induced by cecal ligation puncture (CLP). After 12h, liver was taken for thiobarbituric acid reactive species (TBARS) measurement, δ-aminolevunic acid dehydratase (δ-ALA-D), Cu/Zn superoxide dismutase (Cu/Zn SOD) and catalase (CAT) activities assay. The sepsis increased TBARS, inhibited δ-ALA-D, activated Cu/Zn SOD and had a tendency to decrease CAT activity. However, (PhSe)2 prevented the TBARS formation, but did not prevent the inhibition of δ-ALA-D activity in the animals with damage. Thus, this study showed that (PhSe)2 partially prevents the oxidative stress induced by sepsis, indicating the potential of this compound as a treatment for this pathology. Nevertheless, more tests should be performed to confirm the hypothesis suggested here. [Copyright &y& Elsevier]
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- 2011
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19. Cadmium inhibits δ-aminolevulinate dehydratase from rat lung in vitro: Interaction with chelating and antioxidant agents
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Luchese, Cristiane, Zeni, Gilson, Rocha, João B.T., Nogueira, Cristina W., and Santos, Francielli W.
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CADMIUM , *AMINO compounds , *RATS , *LUNGS , *DITHIOLE - Abstract
Abstract: The effect of cadmium (Cd2+) on δ-aminolevulinate dehydratase (δ-ALA-D) activity from rat lung in vitro was investigated. δ-ALA-D activity, a parameter for metal intoxication, has been reported as a target of Cd2+ in different tissues. The protective effect of monotherapies with dithiol chelating (meso-2,3-dimercaptosuccinic acid (DMSA) and 2,3-dimercaptopropane-1-sulfonic acid (DMPS)) or antioxidant agents (ascorbic acid, diphenyl diselenide (PhSe)2, and N-acetylcysteine (NAC)) was evaluated. The effect of a combined therapy (dithiol chelating×antioxidant agent) was also studied. Zinc chloride (ZnCl2) and dithiothreitol (DTT) were used to investigate the mechanisms involved in cadmium, chelating and antioxidant effects on δ-ALA-D activity. Cadmium inhibited rat lung δ-ALA-D activity at low concentrations. DTT (3mM), but not ZnCl2 (100μM), protected the inhibition of enzyme activity caused by Cd2+. Chelating agents were not effective in restoring the enzyme activity. DMPS and DMSA presented inhibitory effect on enzyme activity. DTT restored the inhibition caused by both chelating agents, but ZnCl2 restored only the inhibitory effect induced by DMSA. These compounds caused a marked potentiation of δ-ALA-D inhibition induced by Cd2+. ZnCl2 did not restore inhibition of enzyme activity caused by Cd2+ plus chelating agents. Conversely, DTT restored the inhibition induced by Cd2+/DMSA, but not by Cd2+/DMPS. Antioxidants were not effective in ameliorating δ-ALA-D inhibition induced by Cd2+, whereas ascorbic acid potentiated the enzyme inhibition induced by this metal. A combined effect of Cd2+ ×DMPS×(PhSe)2 and Cd2+ ×DMPS×NAC was observed. There was no combined effect of Cd2+ ×chelator×antioxidants when DMSA was used. This study demonstrated that Cd2+inhibited δ-ALA-D activity and chelating and antioxidant agents, alone or combined, did not restore the enzyme activity. In contrast, these compounds potentiated the inhibition induced by Cd2+ in rat lung. [Copyright &y& Elsevier]
- Published
- 2007
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20. Avaliação das propriedades biológicas de extratos e compostos de duas espécies de plantas medicinais
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Hacke, Ana Carolina Mendes, Universidade Estadual de Ponta Grossa, Universidade Federal de Santa Maria, Pereira, Romaiana Picada, Marques, Jacqueline Aparecida, Miyoshi, Edmar, Iulek, Jorge, Viana, Adriano Gonçalves, and Rocha, João Batista Teixeira
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antioxidant ,antioxidante ,CIENCIAS EXATAS E DA TERRA::QUIMICA [CNPQ] ,citotoxicidade ,Cannabis sativa ,anxiety ,zebrafish ,ansiedade ,Cymbopogon citratus ,peixe-zebra ,cytotoxicity ,epilepsy ,geraniol ,citral ,epilepsia - Abstract
Submitted by arlindo kohlrausch (ajfk@uepg.br) on 2022-03-04T13:45:29Z No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) Ana Carolina Mendes Hacke.pdf: 5783037 bytes, checksum: 915daf9b077c3b39f5c62d3241cddfe7 (MD5) Made available in DSpace on 2022-03-04T13:45:29Z (GMT). No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) Ana Carolina Mendes Hacke.pdf: 5783037 bytes, checksum: 915daf9b077c3b39f5c62d3241cddfe7 (MD5) Previous issue date: 2021-09-30 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior As plantas medicinais são utilizadas na prevenção de doenças desde o início da civilização humana e as suas propriedades terapêuticas estão relacionadas à composição química de seus extratos brutos. A Cymbopogon citratus (C. citratus), popularmente conhecida como capim- limão, é utilizada em vários países devido à sua ação no sistema nervoso central. Entretanto, apesar dos inúmeros efeitos terapêuticos das plantas medicinais, é comprovado que alguns extratos podem ser potencialmente tóxicos para os seres humanos. Desta forma, é importante a avaliação da possível toxicidade exercida por extratos e compostos relacionados da C. citratus. Neste estudo, a citotoxicidade de extratos e frações obtidos a partir de diferentes métodos de extração, assim como o óleo essencial e seus principais constituintes químicos, citral e geraniol, foi avaliada pelo ensaio de letalidade frente à Artemia salina, e a células sanguíneas humanas (leucócitos e eritrócitos). As frações acetato de etila obtidas em meios ácido e básico, e após a prévia remoção do óleo essencial das folhas da planta, reduziram a viabilidade celular dos leucócitos. Além disso, o óleo essencial, citral e geraniol também foram citotóxicos para estas células na concentração mais alta avaliada. Estas amostras aumentaram a fragilidade osmótica dos eritrócitos, e as análises de microscopia eletrônica de varredura por emissão de campo (MEV-FEG) revelaram que houve alterações na morfologia destas células. Neste trabalho, as atividades ansiolítica e anticonvulsivante do extrato hidroalcoólico e do óleo essencial de C. citratus, do citral e do geraniol (isolados e em associação) foram avaliadas em peixe-zebra. O teste claro/escuro demonstrou que o tratamento prévio com as amostras aumentou o tempo de permanência no lado claro do aquário pelos animais, assim o tempo de latência para a primeira convulsão induzida por pentilenotetrazol (PTZ), indicando ação ansiolítica e anticonvulsivante, respectivamente. A mistura entre citral e geraniol nas menores concentrações investigadas em cada teste também apresentou efeito significativo, que foi, todavia, bloqueados quando os animais foram previamente expostos a uma solução de flumazenil (FMZ), o que revela o envolvimento dos receptores GABAA no mecanismo de ação dos compostos estudados. Além disso, o tratamento prévio dos animais com as amostras restaurou os níveis de malondialdeído (MDA), catalase (CAT), óxido nítrico (NO) e glutationa (GSH) nos homogenatos de cérebro após a exposição dos peixes ao PTZ. Neste estudo, a atividade antioxidante da Cannabis sativa (C. sativa), uma planta utilizada para fins recreativos e medicinais em alguns países, e dos seus principais constituintes químicos, canabidiol (CBD) e tetrahidrocanabinol (THC) (isolados e em associação) também foi investigada. Neste sentido, métodos espectrofotométricos (poder redutor, e sequestro dos radicais 2,2-difenil-1-picril-hidrazil (DPPH• ), 2,2-azinobis(3- etilbenzotiazolina-6-ácido sulfônico) (ABTS•+ ) e ácido hipocloroso (HOCl)), e métodos eletroquímicos (voltametria cíclica e voltametria de pulso diferencial) foram empregados para a avaliação da atividade antioxidante. Todas as amostras exibiram considerável efeito antioxidante em todos os métodos utilizados. Além disso, foi observado efeito sinérgico entre estes canabinóides na atividade antioxidante. Análises de correlação de Pearson demonstraram uma boa correlação entre os resultados obtidos pelos métodos espectrofotométricos e eletroquímicos, o que indicou que estas técnicas são úteis na avaliação da atividade antioxidante de canabinóides. Assim, os resultados obtidos na presente tese reforçaram a importância das plantas medicinais na descoberta de novos fármacos assim como comprovaram as suas propriedades terapêuticas. Medicinal plants have been employed in the prevention of diseases since the beginning of human civilization, and their therapeutic properties are related with the chemical composition of their crude extracts. Cymbopogon citratus (C. citratus), popularly known as lemongrass, is worldwide consume due to its action on the central nervous system. However, despite the therapeutic effects of medicinal plants to humans, it has already proven that some extracts can be exhibit some toxicity. In this way, it is important to evaluate the toxicity of its extracts and related compounds. In this study, the toxicity of C. citratus extracts and fractions obtained from different extraction procedures, as well for essential oil and its main chemical compounds, citral and geraniol, was evaluated in Artemia salina, and in human blood cells (leukocytes and erythrocytes). The ethyl acetate fractions obtained in acidic and basic conditions after essential oil removal from plant leaves, reduced the cell viability of leukocytes. Furthermore, the essential oil, citral and geraniol were also cytotoxic to these cells at the highest concentration analyzed. These samples also increased the osmotic fragility of erythrocytes, and field emission scanning electron microscopy (FESEM) analyzes revealed changes in the erythrocytes morphology. In this work, the anxiolytic and anticonvulsant effects of C. citratus hydroalcoholic extract and essential oil, citral and geraniol (isolated and in association) were evaluated in zebrafish. The light/dark test demonstrated that pretreatment with the samples increased the time spent by the animals in the light side of the tank and increased the latency time for the first seizure induced by pentylenetetrazole (PTZ), indicating anxiolytic and anticonvulsant effects, respectively. The mixture between citral and geraniol at the lowest concentrations employed in each test also showed a significant effect. These effects were antagonized when animals were previous exposed to flumazenil (FMZ) solution, which revealed the involvement of GABAA receptors in the effects. Moreover, pretreatment with samples restored malondialdehyde (MDA), catalase (CAT), nitric oxide (NO) and glutathione (GSH) levels in zebrafish brain homogenates after PTZ exposure. In this study, the antioxidant activity of Cannabis sativa (C. sativa), a medicinal plant used for recreational and medicinal purposes in some countries, and its major constituents, cannabidiol (CBD) and tetrahydrocannabinol (THC) (isolated and in association) was also investigated. Therefore, spectrophotometric (reducing power ability, 2,2-diphenil-1-picryl-hydrazyl (DPPH), 2,2- azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and hypochlorous acid (HOCl) scavenger assays), and electrochemical assays (cyclic voltammetry and differential pulse voltammetry) were employed. All samples exhibited a significant antioxidant effect in the assays used in this study. Furthermore, a synergistic effect between these cannabinoids in the antioxidant activity was verified. Pearson’s correlation analysis showed a good correlation between the results obtained by spectrophotometric and electrochemical assays, which indicated that these techniques can be employed in the evaluation of samples containing cannabinoids. Thus, the results obtained in the present thesis evidenced the importance of medicinal plants in the discovery of new drugs and their therapeutic properties.
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- 2021
21. Synthesis and biological evaluation of new nitrogen-containing diselenides.
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Nascimento, Vanessa, Ferreira, Natasha L., Canto, Rômulo F.S., Schott, Karen L., Waczuk, Emily P., Sancineto, Luca, Santi, Claudio, Rocha, João B.T., and Braga, Antonio L.
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ORGANOSELENIUM compounds , *ANTIOXIDANTS , *DRUG development , *GLUTATHIONE peroxidase , *CHEMICAL synthesis , *STRUCTURE-activity relationship in pharmacology , *NUCLEAR magnetic resonance spectroscopy - Abstract
The antioxidant properties of organoselenium compounds have been extensively investigated with the aim of developing new drugs, since oxidative stress is responsible for a variety of chronic human diseases. Herein, we reported the synthesis of new nitrogen-containing diselenides by a simple and efficient synthetic route. The products were obtained in good to excellent yields and their identification and characterization were achieved by NMR and HRMS techniques. The new derivatives may represent promising structures with different biological activities, which can act against oxidative stress through diverse mechanisms of action. The glutathione peroxidase-like assay (GPx-like activity) of the new synthesized compounds indicated that they reduced H 2 O 2 to water at the expense of PhSH. The best results were obtained with diselenide 2b , which was 9 times more active than the standard organoselenium drug ebselen and, in contrast, this compound was not reduced by hepatic TrxR. All of the new compounds inhibited Fe(II)-induced TBARS. [ABSTRACT FROM AUTHOR]
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- 2014
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22. JM-20 as multi-target compound: evaluation of antioxidant potential, cholinesterase inhibitor, and cytotoxicity
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Silva, Fernanda D’Avila da, Rocha, João Batista Teixeira da, Posser, Thais, Ávila, Daiana Silva de, Fachinetto , Roselei, and Spanevello , Roselia Maria
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Colinesterase ,Toxicity ,Análise computacional ,Antioxidante ,JM-20 ,Toxicidade ,Cholinesterase ,Antioxidant ,Computational analysis ,CIENCIAS BIOLOGICAS::BIOQUIMICA [CNPQ] - Abstract
Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul - FAPERGS Multi-target compounds have aroused the interest of many researchers. The main characteristic of these substances is the ability to act through different mechanisms of action, a relevant fact in cases of pathologies caused by multiple causes. In this context, in some cases of neurodegenerative diseases, a neuronal loss may occur in certain brain regions that contain cholinergic neurons, consequently causing impairment of cognitive functions. Oxidative stress is characterized by the imbalance between the production of reactive species and antioxidant defenses and can be directly related to the causes or consequences of pathologies related to the CNS. Previous studies have shown that JM-20, 1,5-benzodiazepine fused to a dihydropyridine fraction, has different pharmacological properties of clinical interest. In this sense, the main objective of this study was to evaluate the effect of JM-20 on AChE and BChE from different sources, identify the type of enzyme inhibition and understand the interactions between the compound and the enzymes using silicon molecular docking tools. Besides, to verify the protective effect on oxidative stress induced by Fe2+ in leukocytes and to determine the scavenger activity of free radicals. Likewise, investigate possible cytotoxicity using human blood cells and predict ADMET parameters using in silico virtual screening tools. The BChE used was purified from Equus ferus and present in human plasma, while AChE was from Electrophorus electricus, total erythrocytes and present in membranes isolated from human erythrocytes (ghost). The enzymes were pre-incubated for 30 minutes in the presence of different concentrations of JM-20 (1 nM - 200 μM). To assess the type of enzyme inhibition, a kinetic study was performed varying the concentration of the substrate (0.05 - 1.6 mM). Human blood was obtained from healthy volunteers. Immediately after blood collection, the leukocytes or erythrocytes were isolated, washed, and treated with different concentrations of JM-20 and evaluated according to each specific test. The results demonstrated the potential inhibitory effect on AChE activity. These effects were observed in all enzymes tested (IC50 = 123 nM ± 0.2 for E. electricus, 172 nM ± 0.2 for total erythrocytes and 158 nM ± 0.1 for ghost). Besides, we suggest that the compound has a mixed type of inhibition as it changes the Km and Vmax of AChE. Molecular docking demonstrated the existence of eight different isomers of JM-20, and the 4R isomers interact better with HsAChE. The TBARS result points to a potent antioxidant and scavenger effect of free radicals seen in the slow phase of the reaction. However, exposure to all tested JM-20 concentrations (10-50 μM) caused a significant increase in the levels of reactive intracellular species (RS). Although decreased cell viability and increased RS production have been observed, exposure to JM-20 (10-50 μM) did not alter the cell cycle, nor did it cause hemolysis. Analyzes of virtual screening of the JM-20 demonstrated a similar ADMET profile to nifedipine. Thus, our findings support the potential clinical use of JM-20, for the treatment of pathologies associated with the CNS. Compostos multialvo tem despertado o interesse de muitos pesquisadores. Estas substâncias tem como principal característica a capacidade de agir através de diferentes mecanismos de ação, fato relevante em casos de patologias originadas por múltiplas causas. Neste contexto, em alguns casos de doenças neurodegenerativas pode ocorrer a perda neuronal em determinadas regiões cerebrais as quais contem neurônios colinérgicos, consequentemente causando comprometimento de funções cognitivas. O estresse oxidativo é caracterizado pelo desequilíbrio entre a produção das espécies reativas e as defesas antioxidantes e pode estar diretamente relacionado as causas ou consequências de patologias relacionadas ao SNC. Estudos anteriores mostraram que o JM-20, 1,5-benzodiazepina fundida a uma fração de di-hidropiridina, tem diferentes propriedades farmacológicas de interesse clínico. Neste sentido, o objetivo principal deste estudo foi avaliar o efeito do JM-20 na AChE e na BChE de diferentes fontes, identificar o tipo de inibição enzimática e compreender as interações entre o composto e as enzimas utilizando ferramentas in sílico de docking molecular. Além disso, verificar o efeito protetor no estresse oxidativo induzido por Fe2+ em leucócitos e determinar a atividade scavenger de radicais livres. Do mesmo modo, averiguar a possível citotoxicidade utilizando células sanguíneas humanas e predizer parâmetros ADMET utilizando ferramentas in sílico de screening virtual. A BChE utilizada foi purificada de Equus ferus e presente no plasma humano, enquanto que a AChE foi de Electrophorus electricus, eritrócitos totais e presente nas membranas isoladas de eritrócitos humanos (ghost). As enzimas foram pré-incubadas durante 30 minutos na presença de diferentes concentrações de JM-20 (1 nM - 200 μM). Para avaliar o tipo de inibição enzimática, foi realizado um estudo cinético variando a concentração do substrato (0,05 - 1,6 mM). O sangue humano foi obtido de voluntários saudáveis. Imediatamente após a coleta do sangue, os leucócitos ou eritrócitos foram isolados, lavados e tratados com diferentes concentrações de JM-20 e avaliados de acordo com cada teste específico. Os resultados demonstraram o potencial efeito inibitório na atividade da AChE. Estes efeitos foram observados em todas as enzimas testadas (IC50 = 123 nM ± 0,2 para E. electricus, 172 nM ± 0,2 para eritrócitos totais e 158 nM ± 0,1 para ghost). Além disso, sugerimos que o composto apresenta um tipo misto de inibição já que altera o Km e Vmax da AChE. O docking molecular demonstrou a existência de oito isômeros diferentes do JM-20 e os isômeros 4R interagem melhor com a HsAChE. O resultado do TBARS aponta para um potente efeito antioxidante e efeito scavenger de radicais livres observados na fase lenta da reação. Entretanto, a exposição a todas as concentrações de JM-20 testadas (10-50 μM) causou um aumento significativo nos níveis de espécies reativas intracelulares (ER). Embora tenha sido observada diminuição da viabilidade celular e aumento da produção de ER, a exposição ao JM-20 (10-50 μM) não alterou o ciclo celular, assim como não causou hemólise. Análises de screening virtual do JM-20 demonstraram similar perfil ADMET a nifedipina. Assim, nossas descobertas apoiam o potencial uso clínico do JM-20, para o tratamento de patologias associadas ao SNC.
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- 2020
23. Copper and selenium: Auxiliary measure to control infection by Haemonchus contortus in lambs.
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do Rêgo Leal, Marta Lizandra, Lamberti Pivoto, Felipe, Costa Fausto, Guilherme, Rodrigues Aires, Adelina, Grando, Thirssa Helena, Roos, Daniel Henrique, Sudati, Jéssie Haigert, Wagner, Caroline, Machado Costa, Márcio, Molento, Marcelo Beltrão, and Teixeira da Rocha, João Batista
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PHYSIOLOGICAL effects of copper , *PHYSIOLOGICAL effects of selenium , *PARASITIC diseases , *OXIDATIVE stress , *HAEMONCHUS contortus , *ANTIOXIDANTS , *SODIUM selenite , *ANIMAL models in research - Abstract
The aim of this study was to evaluate the effects of selenium and copper on oxidative stress and its performance in lambs experimentally infected with Haemonchus contortus. Twenty-eight five-months old lambs were experimentally infected by the oral route with 5000 third-stage infective larvae and allocated into four groups, i.e., untreated animals, animals treated intramuscularly with sodium selenite (0.2 mg kg-1), animals treated subcutaneously with copper (3.5 mg kg-1), and animals treated with sodium selenite (IM; 0.2 mg kg-1) and copper (SC; 3.5 mg kg-1). These animals received oat hay (Avena sativa) and commercial concentrate, totaling 15% of crude protein, 30% being derived from oat hay and 70% of the concentrate. Lipid peroxidation, antioxidant enzymes, eggs per gram of feces (EPG) and body weight were assessed on the day of infection and after 20, 40, 60 and 80 days post-infection. The number of H. contortus adults was assessed at the end of the experiment. The selenium associated or not with copper reduced the effects of oxidative stress caused by infection. The groups supplemented with copper had increased body weight, and the combination of these two minerals reduced the EPG and number of H. contortus adults in lambs. The use of selenium associated with copper may help the control of infection by H. contortus. [ABSTRACT FROM AUTHOR]
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- 2014
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24. Phytochemical constituents, antioxidant activity, cytotoxicity and osmotic fragility effects of Caju (Anacardium microcarpum).
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Filho, Valter Menezes Barbosa, Waczuk, Emily Pansera, Kamdem, Jean Paul, Abolaji, Amos Olalekan, Lacerda, Sirleis Rodrigues, da Costa, José Galberto Martins, de Menezes, Irwin Rose Alencar, Boligon, Aline Augusti, Athayde, Margareth Linde, da Rocha, João Batista Teixeira, and Posser, Thaís
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ANTIOXIDANTS , *CELL-mediated cytotoxicity , *CASHEW nuts , *ANACARDIUM , *BOTANICAL chemistry , *PHYTOCHEMICALS - Abstract
Highlights: [•] Anacardium microcarpum fractions showed significant DPPH scavenging activity. [•] The fractions inhibited Fe2+-induced LPO in brain and liver homogenates. [•] The fractions were not cytotoxic to leukocytes and prevented H2O2-induced cytotoxicity. [•] The fractions did not have any effect on human erythrocytes osmotic fragility. [•] A. microcarpum showed the presence of phenolics and flavonoids compounds as major phytochemical groups. [Copyright &y& Elsevier]
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- 2014
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25. The antioxidant properties of different phthalocyanines
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Amaral, Guilherme Pires, Puntel, Gustavo Orione, Dalla Corte, Cristiane Lenz, Dobrachinski, Fernando, Barcelos, Rômulo Pillon, Bastos, Luiza Lena, Ávila, Daiana Silva, Rocha, João Batista Teixeira, da Silva, Edegar Ozorio, Puntel, Robson Luiz, and Soares, Félix Alexandre Antunes
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PHTHALOCYANINES , *ANTIOXIDANTS , *OXIDATIVE stress , *ETIOLOGY of diseases , *LABORATORY mice , *REACTIVE oxygen species , *NITRIC oxide , *SERUM albumin , *NEURODEGENERATION - Abstract
Abstract: Oxidative stress is involved in the etiology of several chronic diseases, including cardiovascular disease, diabetes, cancer, and neurodegenerative disorders. From this perspective, we have evaluated the possible antioxidant capacities of five different phthalocyanines (PCs), consisting of four metallophthalocyanines (MPCs) and one simple phthalocyanine (PC) in order to explore, for the first time, the potential antioxidant activities of these compounds. Our results show that all PCs tested in this study have significant antioxidant activity in lipid peroxidation assay, providing protection from sodium nitroprusside -induced oxidative damage to supernatant from the homogenized liver, brain, e rim of mice. Compared to the non-induced control, the PCs were generally more efficient in reducing malondialdehyde levels in all assays on lipid peroxidation induced by sodium nitroprusside; the order of approximate decrease in efficiency was as follows: manganese-PC (better efficiency)>copper-PC>iron-PC>zinc-PC>PC (worst efficiency). Furthermore, the copper-PC and manganese-PC compounds exerted a significant protective effect in deoxyribose degradation assays, when employing Fe2+, Fe2+ +H2O2, and H2O2 solutions. In conclusion, all PCs tested here were shown to be promising compounds for future in vivo investigations, because of their potential antioxidant activities in vitro. [Copyright &y& Elsevier]
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- 2012
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26. Protective effect of Melissa officinalis aqueous extract against Mn-induced oxidative stress in chronically exposed mice
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Martins, Eduarda N., Pessano, Naira T.C., Leal, Luiza, Roos, Daniel H., Folmer, Vanderlei, Puntel, Gustavo O., Rocha, João Batista Teixeira, Aschner, Michael, Ávila, Daiana Silva, and Puntel, Robson Luiz
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LEMON balm , *OXIDATIVE stress , *LABORATORY mice , *MANGANESE , *NEURODEGENERATION , *PARKINSON'S disease , *NEUROTOXICOLOGY , *CEREBELLUM - Abstract
Abstract: Manganese (Mn) is an essential element for biological systems; however occupational exposure to high levels of this metal may lead to neurodegenerative disorders, resembling Parkinson''s disease (PD). While its mechanisms of neurotoxicity have yet to be fully understood, oxidative stress plays a critical role. Thus, the main goal of this study was to investigate the efficacy of aqueous extract of Melissa officinalis in attenuating Mn-induced brain oxidative stress in mice. Sixteen male mice were randomly divided into two groups and treated for 3 months: the first group consumed tap water (control group) and the second group was treated with Mn (50mg/kg/day for habituation during the first 15 days followed by 100mg/kg/day for additional 75 days) in the drinking water. After 3 months both groups were sub divided (n =4 per group) and treated for additional 3 months with Mn and/or M. officinalis in the drinking water. The first group (control) was treated with water and served as control; the second group (M. officinalis) was treated with M. officinalis (100mg/kg/day); the third group was treated with Mn (100mg/kg/day); the fourth group (Mn+ M. officinalis) was treated with both Mn and M. officinalis (100mg/kg/day each). Mn-treated mice showed a significant increase in thiobarbituric acid reactive species (TBARS) levels (a marker of oxidative stress) in both the hippocampus and striatum. These changes were accompanied by a decrease in total thiol content in the hippocampus and a significant increase in antioxidant enzyme activity (superoxide dismutase and catalase) in the hippocampus, striatum, cortex and cerebellum. Co-treatment with M. officinalis aqueous extract in Mn-treated mice significantly inhibited the antioxidant enzyme activities and attenuated the oxidative damage (TBARS and decreased total thiol levels). These results establish that M. officinalis aqueous extract possesses potent antioxidative properties, validating its efficacy in attenuating Mn-induced oxidative stress in the mouse brain. [Copyright &y& Elsevier]
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- 2012
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27. Butane-2,3-dionethiosemicarbazone: An oxime with antioxidant properties
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Puntel, Gustavo Orione, de Carvalho, Nelson Rodrigues, Gubert, Priscila, Palma, Aline Schwertner, Corte, Cristiane Lenz Dalla, Ávila, Daiana Silva, Pereira, Maria Ester, Carratu, Vanessa Santana, Bresolin, Leandro, da Rocha, João Batista Teixeira, and Soares, Félix A. Antunes
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OXIMES , *ANTIOXIDANTS , *ACETYLCHOLINESTERASE , *ENZYME inhibitors , *HYDROGEN peroxide , *CHEMICAL reactions - Abstract
Abstract: Oximes are compounds generally used to reverse the acetylcholinesterase (AChE) inhibition caused by organophosphates (OPs). The aim of this study was to examine the capacity of the butane-2,3-dionethiosemicarbazone oxime to scavenge different forms of reactive species (RS) in vitro, as well as counteract their formation. The potential antioxidant and toxic activity of the oxime was assayed both in vitro and ex vivo. The obtained results indicate a significant hydrogen peroxide (H2O2), nitric oxide (NO) and 1,1-diphenyl-2-picrylhydrazyl (DPPH scavenging activity at 0.275, 0.5 and 5μM of oxime, respectively (p ≤0.05). The oxime exhibited a powerful inhibitory effect on dihydroxybenzoate formation (25μM) (p ≤0.05) and also decreased deoxyribose degradation induced by Fe2+ and via Fenton reaction (0.44 and 0.66mM, respectively) (p ≤0.05). The oxime showed a significant inhibitory effect on σ-phenantroline reaction with Fe2+ (0.4mM) suggesting a possible interaction between the oxime and iron. A significant decrease in the basal and pro-oxidant-induced lipid peroxidation in brain, liver, and kidney of mice was observed both in vitro and ex vivo (p ≤0.05). In addition, in our ex vivo experiments the oxime did not depict any significant changes in thiol levels of liver, kidney and brain as well as did not modify the δ-aminolevulinate dehydratase (δ-ALA-D) activity in these tissues. Taken together our results indicate an in vitro and ex vivo antioxidant activity of the oxime possibly due to its scavenging activity toward different RS and a significant iron interaction. [Copyright &y& Elsevier]
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- 2009
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28. An organotellurium compound with antioxidant activity against excitotoxic agents without neurotoxic effects in brain of rats
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Ávila, Daiana Silva, Gubert, Priscila, Palma, Aline, Colle, Dirleise, Alves, Diego, Nogueira, Cristina Wayne, Rocha, João Batista Teixeira, and Soares, Félix Alexandre Antunes
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ORGANOTELLURIUM compounds , *NEURODEGENERATION , *ANTIOXIDANTS , *PEROXIDATION - Abstract
Abstract: The glutamatergic system is an important target in many neurodegenerative diseases and for several neurotoxic drugs. Organotellurium compounds are often very good free radical scavengers’ agents. Recently, we reported that diethyl-2-phenyl-2-tellurophenyl vinylphosphonate is a compound with low toxicity in vitro and in vivo, as well as also possesses antioxidant activity against iron-induced lipid peroxidation. The aim of this study was to evaluate in vitro the antioxidant and mitochondrial protective effect of this organotellurium compound against quinolinic acid (QA) and sodium nitroprusside (SNP), and to evaluate the in vitro actions of this organotellurium compound in the glutamatergic system in brain of rats. We observed that the telluro vinylphosphonate possess an antioxidant activity against QA and SNP at micromolar concentrations. When tested at antioxidant concentrations (from 2 to 10μM), the compound does not affect the mitochondrial viability and [3H]glutamate uptake in slices from cerebral cortex, hippocampus and striatum, [3H]glutamate release from synaptosomal preparations and [3H]glutamate binding in membrane preparation. Our data suggest that the telluro vinylphosphonate act as an antioxidant in the central nervous system in vitro with no effects on the glutamatergic system; nevertheless more studies in different models of brain injury must be performed in order to corroborate our findings. [Copyright &y& Elsevier]
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- 2008
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29. Sub-chronic administration of diphenyl diselenide potentiates cadmium-induced testicular damage in mice
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Santos, Francielli W., Graça, Dominguita L., Zeni, Gilson, Rocha, João B.T., Weis, Simone N., Favero, Alexandre M., and Nogueira, Cristina W.
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MICE , *BODY weight , *ENDOCRINE glands , *PEROXIDATION - Abstract
Abstract: Sub-chronic cadmium (Cd) exposure causes testicular damage in mice. The mode of action may involve oxidative stress and especially lipid peroxidation. The present study has monitored the pathogenesis of testicular damage during sub-chronic Cd exposure and has evaluated the potential protective effect of antioxidant therapy with diphenyl diselenide (PhSe)2. Male mice were dosed with 2.5mg/kg CdCl2 (2.5mg/kg) with or without (PhSe)2 (5μmol/kg) at 30min post-exposure using a model of five weekly subcutaneous injections. Histological evaluation of the testis was performed across a 4 week test period. Animals exposed to CdCl2 and CdCl2 plus (PhSe)2 displayed a reduction in body weight gain and testicular weight. Progressive damage and histolopathological changes in the testis were not remediated with, but rather were potentiated by, (PhSe)2 therapy. We conclude that (PhSe)2 enhances testicular injury in an animal model for sub-chronic Cd exposure mice. [Copyright &y& Elsevier]
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- 2006
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30. Effects of diphenyl–diselenide on orofacial dyskinesia model in rats
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Burger, Marilise E., Fachinetto, Roselei, Wagner, Caroline, Perottoni, Juliano, Pereira, Romaiana P., Zeni, Gilson, and Rocha, João B.T.
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IATROGENIC diseases , *TARDIVE dyskinesia , *GLUTATHIONE , *METALLOENZYMES - Abstract
Abstract: Recently, we have described the beneficial effects of Diphenyl diselenide, an organochalcogen with glutathione peroxidase-like activity, on reserpine-induced orofacial dyskinesia in old rats. In this study, our aim was to examine the effects of diselenide on haloperidol-induced orofacial dyskinesia in rats. Male wistar rats received one single dose of Haloperidol decanoate (57mg/kg/im) or control. After this dose, the animals received daily administration of diphenyl diselenide (1, 5 or 10mg/kg/sc) or control, during 28 days. Twenty-four hours after the last diselenide or control solution injection, all the rats were observed for quantification of oral dyskinesia through the frequency of vacuous chewing movements (VCM) and tongue protrusion (TP) and the duration of facial twitching (FT). Haloperidol caused a significant increase in VCM, TP and FT observed in the 4 weekly evaluations (p <0.05). The co-administration of diselenide (5mg/kg) reversed this effect for all the parameters in four behavioral sessions. The results of the present study demonstrate the possible protective activity of diphenyl diselenide on haloperidol-induced orofacial diskinesia. This effect is in accordance to the involvement of neurotoxicity in orofacial dyskinesia and suggest that studies be continued with new antioxidant compounds. [Copyright &y& Elsevier]
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- 2006
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31. Acute liver damage induced by 2-nitropropane in rats: Effect of diphenyl diselenide on antioxidant defenses
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Borges, Lysandro P., Nogueira, Cristina Wayne, Panatieri, Rodrigo B., Rocha, João Batista Teixeira, and Zeni, Gilson
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BILIARY tract , *VITAMIN C , *NITROGEN excretion , *METABOLISM - Abstract
Abstract: The effect of post-treatment with diphenyl diselenide on liver damage induced by 2-nitropropane (2-NP) was examined in male rats. Rats were pre-treated with a single dose of 2-NP (100mg/kg body weight dissolved in canola oil). Afterward, the animals were post-treated with a dose of diphenyl diselenide (10, 50 or 100μmol/kg). The parameters that indicate tissue damage such as liver histopathology, plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyl transferase (GGT), urea and creatinine were determined. Since the liver damage induced by 2-NP is related to oxidative damage, lipid peroxidation, superoxide dismutase (SOD), catalase (CAT) and ascorbic acid level were also evaluated. Diphenyl diselenide (50 and 100μmol/kg) effectively restored the increase of ALT and AST activities and urea level when compared to the 2-NP group. At the higher dose, diphenyl diselenide decreased GGT activity. Treatment with diphenyl diselenide, at all doses, effectively ameliorated the increase of hepatic and renal lipid peroxidation when compared to 2-NP group. 2-NP reduced CAT activity and neither alter SOD activity nor ascorbic acid level. This study points out the involvement of CAT activity in 2-NP-induced acute liver damage and suggests that the post-treatment with diphenyl diselenide was effective in restoring the hepatic damage induced by 2-NP. [Copyright &y& Elsevier]
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- 2006
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32. Ebselen and diphenyl diselenide do not change the inhibitory effect of lead acetate on delta-aminolevulinate dehidratase
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Perottoni, Juliano, Meotti, Flavia C., Folmer, Vanderlei, Pivetta, Lucinéia, Nogueira, Cristina W., Zeni, Gilson, and Rocha, João B.T.
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BIPHENYL compounds , *BENZOBIPHENYLENES , *DICHLOROBENZIDINE , *ABDOMEN - Abstract
Abstract: It is known that lead is toxic to several species of animals, and growing data support the participation of oxidative in lead toxicity. Selenium compounds, like diphenyl diselenide and Ebselen have a thiol-peroxidase like and other antioxidant properties. In this work, we determine whether these non-thiol-containing compounds with antioxidant properties could reverse the toxicity produced by Pb2+. Lead acetate injection followed by injection with Ebselen or diphenyl diselenide did not change the levels of non-protein thiol groups (NPSH), whereas simultaneous treatment with lead plus Ebselen reduced NPSH levels in liver. Lead and Ebselen caused a marked reduction in TBARS level in kidney, whereas lead or selenium compounds did not change TBARS levels in brain or liver. Lead acetate inhibited, δ-aminolevulinate dehydratase (ALA-D) activity in blood, liver, kidney and brain. Selenium compounds did not change enzyme activity nor the inhibitory effect of lead acetate in kidney and liver. Ebselen reversed brain ALA-D inhibition caused by Pb2+. Reactivation index for ALA-D by DTT was higher in lead-treated groups than control groups in all tissues. Lead acetate or selenium compounds did not demonstrate alteration on [3H]-glutamate uptake by synaptosomes, whereas lead acetate plus Ebselen showed an increase on [3H]-glutamate uptake. The results of the present study indicate that ALA-D inhibition antecedes the overproduction of reactive oxygen species, which is becoming well documented in the literature. [Copyright &y& Elsevier]
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- 2005
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33. Effects of age on reserpine-induced orofacial dyskinesia and possible protection of diphenyl diselenide
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Burger, Marilise, Fachinetto, Roselei, Calegari, Luciano, Paixão, Márcio W., Braga, Antônio L., and Rocha, João B.T.
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SEROTONIN antagonists , *MURIDAE , *IATROGENIC diseases , *TARDIVE dyskinesia , *PATHOLOGICAL physiology , *NEUROTOXICOLOGY - Abstract
Abstract: Acute reserpine administration produces persistent oral dyskinesia in rats, an alleged animal model of tardive dyskinesia. The pathophysiology of the syndrome remains unclear, but experimental evidence suggests that neurodegeneration in the basal ganglia caused by oxidative stress plays a pivotal role in TD development. In this paper, the authors examined whether diphenyl diselenide, an organochalcogen with antioxidant properties, changes the behavioral and neurochemical effect of acute reserpine administration in old rats. The basal vacuous chewing movements (VCMs) and facial twitching (FT) duration was higher in old rats (15 months of age), when compared with adult rats (3 months of age; 0.01). Basal thiobarbituric acid-reactive species (TBARS) levels were increased only in the cortex of old rats, when compared to adult animals (p<.05). Reserpine injection (1mg/kg, s.c. for 3 days every other day) caused a significant increase on the tongue protusion (TP) frequency (p<.01) and facial twitching duration (p<.01) in old rats. Diphenyl diselenide (10mg/kg, i.p. for 4 days, starting the day before reserpine) reversed only reserpine-induced TP increase (p<.01). Reserpine caused a significant increase in striatal TBARS levels (p<.01) and diselenide reversed (p<.01) the effect of reserpine on TBARS levels in the striatum. In subcortical parts, isolated reserpine or diselenide administration significantly increased (p<.01) the levels of TBARS, while simultaneous treatment with reserpine and diselenide reverted this effect (p<.01). The results of the present study confirmed the effects of age on orofacial dyskinesia. Diphenyl diselenide, an organochalcogen with antioxidant properties, showed modest effects on reserpine-induced orofacial dyskinesia. However, additional studies are still necessary to establish whether this compound can be considered an effective antioxidant in other models of neurotoxicity. [Copyright &y& Elsevier]
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- 2004
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34. Cadmium induced testicular damage and its response to administration of succimer and diphenyl diselenide in mice
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Santos, Francielli W., Oro, Tatiana, Zeni, Gilson, Rocha, João B.T., do Nascimento, Paulo C., and Nogueira, Cristina W.
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CADMIUM , *VITAMIN C , *OXYGEN , *TESTIS , *THERAPEUTICS , *MICE - Abstract
Acute effects of cadmium in mice testes were evaluated. Animals received a single dose of CdCl2 (2.5 mg/kg or 5 mg/kg, intraperitoneally) and a number of toxicological parameters in mice testes were examined such as δ-aminolevulinic acid dehydratase (δ-ALA-D) activity, lipid peroxidation, hemoglobin content and components of the antioxidant defenses (superoxide dismutase (SOD) activity and ascorbic acid concentration). Furthermore, a possible protective effect of meso-2,3-dimercaptosuccinic acid (DMSA) and diphenyl diselenide (PhSe)2 are studied. The results demonstrated inhibition of δ-ALA-D and SOD activities, reduction in ascorbic acid, increase of lipid peroxidation induced by cadmium, indicating testes damage. DMSA (400 μmol/Kg) and (PhSe)2 (100 μmol/Kg) protected inhibitory effect of 2.5 mg/kg CdCl2 on δ-ALA-D and restored the increase of TBARS levels. Otherwise, (PhSe)2 treatment was effective in reducing the increase of TBARS levels induced by 5 mg/kg CdCl2, whereas DMSA and (PhSe)2, in combination, were ineffective in reducing TBARS level. However, these compounds alone or in combination, were unable to protect SOD activity and to improve ascorbic acid levels near to the normal value. The use of combined therapy (DMSA plus (PhSe)2) not proved be better than the monotherapy, in improving toxicological parameters evaluated in this model of testicular damage induced by cadmium. [Copyright &y& Elsevier]
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- 2004
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35. Polyamines reduces lipid peroxidation induced by different pro-oxidant agents
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Bellé, Nádia Aléssio Velloso, Dalmolin, Gerusa Duarte, Fonini, Graciela, Rubin, Maribel Antonello, and Rocha, João Batista Teixeira
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POLYAMINES , *AMINES , *LIPIDS , *PEROXIDATION - Abstract
Polyamines, among other functions, are considered to act as a free radical scavenger and antioxidant. The quinolinic acid (QA), sodium nitroprusside (SNP) and iron (Fe+2) stimulate production of free radicals and lipid peroxidation. In the present study, we investigated the free radical and/or aldehyde scavenger effects of polyamines spermine and spermidine on thiobarbituric acid reactive species (TBARS) production induced by QA, SNP, Fe+2/EDTA system and free Fe2+ in rat brain. Spermine and spermidine inhibited QA-induced TBARS production; however spermine was a better antioxidant than spermidine. Spermine also inhibited SNP-, Fe+2/EDTA- and free Fe2+-induced TBARS production, but had a modest effect. Spermidine, in turn, also discreetly inhibited SNP-, Fe+2/EDTA- and free Fe2+-induced TBARS production. In the presence of MK-801, QA-induced TBARS production was considerably more inhibited by polyamines. In addition, arcaine does not affect the reducer effect of polyamines. The present findings suggest that the observed effects of polyamines are not related to the activation of NMDA receptor but with their antioxidant and free radical scavenger properties. [Copyright &y& Elsevier]
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- 2004
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36. Ebselen attenuates reserpine-induced orofacial dyskinesia and oxidative stress in rat striatum
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Burger, Marilise E., Alves, Audrei, Callegari, Luciano, Athayde, Fernanda R., Nogueira, Cristina W., Zeni, Gilson, and Rocha, João B.T.
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ANTIOXIDANTS , *RESERPINE , *MOVEMENT disorders - Abstract
Reserpine-induced orofacial dyskinesia is an alleged animal model of tardive dyskinesia whose pathophysiology has been related to striatal oxidative stress.In the present investigation, the authors examined whether ebselen, an antioxidant organochalcogen with glutathione peroxidase-like activity, changes the behavioral and neurochemical effect of acute reserpine administration. Reserpine injection for 3 days every other day caused a significant increase on the tongue protrusion frequency and ebselen (30 mg/kg ip for 4 days, starting 1 day before reserpine) reversed partially the effect of reserpine (P<.05). Reserpine- and reserpine+ebselen-treated groups displayed an increase in vacuous chewing frequency when compared to control and ebselen-treated groups (P<.05) Reserpine increased the duration of facial twitching and ebselen reversed partially the effect of reserpine (P<.01). Reserpine increased significantly the thiobarbituric acid-reactive species (TBARS) levels, and ebselen reversed the effect of reserpine on TBARS production in rat striatum. The results of the present study clearly indicated that ebselen has a protective role against reserpine-induced orofacial dyskinesia and reversed the increase in TBARS production caused by reserpine administration. Consequently, the use of ebselen as a therapeutic agent for the treatment of tardive dyskinesia should be considered. [Copyright &y& Elsevier]
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- 2003
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37. Ebselen blocks the quinolinic acid-induced production of thiobarbituric acid reactive species but does not prevent the behavioral alterations produced by intra-striatal quinolinic acid administration in the rat
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Rossato, Janine I., Zeni, Gilson, Mello, Carlos F., Rubin, Maribel A., and Rocha, João B.T.
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ORGANIC compounds , *GLUTATHIONE , *ISCHEMIA - Abstract
Ebselen (EBS) is a seleno-organic compound with glutathione peroxidase-like activity which is neuroprotective in acute stroke ischemia. In this study, we investigated the effect of EBS on quinolinic acid (QA)-induced neurotoxicity. EBS inhibited QA-induced production of thiobarbituric acid reactive species (TBARS) by striatal homogenates in vitro with an IC50 of 1.85 μM. Intra-striatal injection of QA (360 nmol) increased striatal content of TBARS and induced convulsions and contralateral rotational behavior. Intra-striatal pre-injection of EBS (10 nmol) 15 min before QA abolished QA-induced TBARS production but did not alter QA-induced behavioral effects. The present findings suggest that EBS acts on post-receptor events, neutralizing free radicals produced by overstimulation of N-methyl-d-aspartate receptors. [Copyright &y& Elsevier]
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- 2002
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38. Triplaris gardneriana seeds extract exhibits in vitro anti-inflammatory properties in human neutrophils after oxidative treatment.
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Lopes Neto, José Joaquim, Silva de Almeida, Thiago, Almeida Filho, Luiz Carlos Pereira, Rocha, Talita Magalhães, Nogara, Pablo Andrei, Nogara, Karise Fernanda, Teixeira da Rocha, João Batista, Almeida Moreira Leal, Luzia Kalyne, and Urano Carvalho, Ana Fontenele
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ANTI-inflammatory agents , *ANTIOXIDANTS , *ENZYME inhibitors , *FLAVONOIDS , *HYDROGEN peroxide , *INFLAMMATION , *MATHEMATICAL models , *NEUTROPHILS , *NONSTEROIDAL anti-inflammatory agents , *PHENOLS , *SEEDS , *SPECTRUM analysis , *TRADITIONAL medicine , *PLANT extracts , *THEORY , *OXIDATIVE stress , *DESCRIPTIVE statistics , *IN vitro studies ,THERAPEUTIC use of plant extracts - Abstract
Triplaris gardneriana Wedd. (Polygonaceae family) is a plant species from Brazilian semiarid region which is used in local traditional medicine for the treatment of inflammatory conditions such as hemorrhoids. In this study, the in vitro anti-inflammatory activity of different concentrations of ethanolic extract from T. gardneriana seeds (EETg) was performed in order to contribute to the knowledge about etnomedicinal use of this plant species. The anti-inflammatory properties were evaluated through different approaches, such as in vitro protein anti-denaturation test, scavenging of reactive oxygen species (ROS) and myeloperoxidase (MPO) inhibition in human neutrophils activated by phorbol-12-myristate-13-acetate (PMA). Besides that, molecular docking was performed to provide new insights about the interaction between the major phenolic components in the plant extract and MPO. EETg was characterized showing a total phenol content of 153.5 ± 6.3 μg gallic acid equivalent/mg extract, ability to remove hydrogen peroxide (H 2 O 2) in a concentration-dependent manner and had a spectroscopic profile which suggests the presence of hydroxyl groups. EETg was able to prevent protein denaturation ranging from 40.17 to 75.09%. The extract, at 10 and 20 μg/mL, was able to modulate neutrophils pro-inflammatory functions, such as degranulation and burst respiratory. In both assays, the EETg had anti-inflammatory effect comparable to nonsteroidal anti-inflammatory drugs. Among the main phenolic compounds of EETg, quercitrin, quercetin and catechin showed the highest binding affinity in silico to MPO. This study demonstrated, for the first time, that the anti-inflammatory effect of T. gardneriana seeds occurs due to its modulatory effect on human neutrophil degranulation and free-radical scavenging activity. • Many of the Brazilian medicinal plants are unknown. • Triplaris gardneriana seeds are a good source of antioxidant molecules. • T. gardneriana extract has in vitro anti-inflammatory properties. • T. gardneriana extract inhibits neutrophil MPO activity. • Molecular docking reveals interaction between phenolic compounds and MPO. [ABSTRACT FROM AUTHOR]
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- 2020
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39. Modified expression of antioxidant genes in lobster cockroach, Nauphoeta cinerea exposed to methylmercury and monosodium glutamate.
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Afolabi, Blessing A., Olagoke, Olawande C., Souza, Diogo O., Aschner, Michael, Rocha, João B.T., and Segatto, Ana Lúcia Anversa
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METHYLMERCURY , *MONOSODIUM glutamate , *COCKROACHES , *LOBSTERS , *SUPEROXIDE dismutase , *HUMAN ecology - Abstract
Methylmercury (MeHg) is a neurotoxicant that poses risk to human health and the environment, while glutamate homeostasis is necessary for the proper functioning of the brain. We have previously shown an increase in oxidative stress after cockroach exposure to diet containing monosodium glutamate (MSG), both separately and combined with a low dose of methylmercury. We herein seek to corroborate these findings by quantifying the expression levels of certain antioxidant genes in Nauphoeta cinerea exposed to MeHg and MSG. Cockroaches were fed with the basal diet alone, basal diet +2% NaCl, basal diet +2% MSG; basal diet +0.125 mg/g MeHg, basal diet +0.125 mg/g MeHg +2% NaCl; and basal diet +0.125 mg/g MeHg +2% MSG for 21 days and mRNA from head homogenate was used to quantify the expression of antioxidant genes such as glutathione-s-transferase (GstS , GstT , GstD), thioredoxin (Trx1 , Trx2 , Trx5), peroxiredoxin (prx4), superoxide dismutase (Sod), catalase (Cat). MeHg, NaCl and MSG alone downregulated mRNA levels of GstS and Trx5 , in contrast, co-exposure of MeHg + MSG, upregulated these genes. MeHg + NaCl upregulated the mRNA levels of C at and S od but these genes were downregulated by NaCl alone. MeHg + NaCl and MeHg + MSG upregulated G stD and Gst T. MeHg alone upregulated the transcription levels of T rx1 , Trx2 and Prx4. The disruptions in the transcription levels of various genes by MeHg and MSG, reinforce the toxicity of these neurotoxicants. In general, the data suggest their additive effects and support the use of N. cinerea as a model for toxicological studies. • MeHg alone downregulated mRNA levels of GstS and Trx 5 in experimental cockroaches. • MeHg + MSG upregulated downregulated mRNA levels of GstS and Trx 5 in exposed cockroaches. • MeHg + NaCl and MeHg + MSG upregulated G stD and Gst T in cockroaches. • ICP-AES analysis showed an increase in mercury (Hg) levels in the MeHg treated groups in the heads of cockroaches. [ABSTRACT FROM AUTHOR]
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- 2020
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40. Mechanisms of methilmercury toxicity: protective effect of flavonoids
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Wagner, Caroline, Rocha, João Batista Teixeira da, Nogueira, Cristina Wayne, Gonçalves, Carlos Alberto Saraiva, Brandão, Ricardo, Franco, Jeferson Luis, and Burger, Marilise Escobar
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Flavonoids ,Flavonóides ,Oxidative stress ,Estresse oxidativo ,Tiorredoxina redutase ,Cálcio ,MeHg ,Antioxidantes ,Calcium ,Antioxidant ,CIENCIAS BIOLOGICAS::BIOQUIMICA [CNPQ] ,Thioredoxin redutase - Abstract
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Methylmercury (MeHg) is an important environmental toxicant that may cause irreversible neurobehavioral and neuropsychological disorders in humans and experimental animals. The major mechanisms of MeHg-induced toxicity currently being explored are the disruption of intracellular calcium homeostasis, the induction of oxidative stress, inhibition of neuronal Na+/K+ -ATPase activity and change the status of antioxidant systems. In addition, recent data reported the involvement of MeHg toxicity with damage in thioredoxin system. On the other hand, flavonoids have been reported to possess divalent metal chelating properties, antioxidant activities and to readily permeate the blood brain barrier. They can also provide neuroprotection in a wide array of cellular and animal models of neurological diseases, including protection against MeHg toxicity. However, the exact mechanism of MeHg toxicity remain unclear and limited data on the interaction of MeHg with flavonoids are avaliable in literature. In view of this, our study evaluated the mechanisms of MeHg toxicity in vivo and in vitro models and evaluated the performance of different flavonoids: quercetin, quercitrin and rutin in diferent models of MeHg toxicity. Our study showed that MeHg (100 μM) caused lipid peroxidation and reactive oxygen species (ROS) generation in brain cortical slices. Quercitrin and quercetin protected against this toxicity and mitochondria from MeHg (5 μM)-induced ROS generation. In contrast, rutin did not afford a significant protective effect against MeHg (100 μM)-induced lipid peroxidation and ROS production in cortical brain slices. MeHg-generated ROS in cortical slices was dependent upon an increase in intracellular calcium levels. In vivo studies with mice treated during 30 days with MeHg (5mg/Kg) orally, presented a marked increase in toxicity parameters (loss in body weight gain, increased in micronucleis frequencies, nefrotoxicity), decrease in motor system performance (locomotor activity and motor coordination) and spatial memory deficiency as well as alteration in some biochemical parameters (decrease in glutathione peroxidase and Na+/K+ ATPase activity, increase in lipid peroxidation). The co-treatment with quercitrin (10mg/kg) intraperitoneally, decreased the behavior alterations manly by decreased lipid peroxidation levels, maintained the Na+/K+ ATPase and GPx activities. In addition, our study demonstrated, for the first time, that MeHg inhibited the activity of thioredoxin reductase. A single oral MeHg administration (1, 5 and 10 mg/Kg) caused a marked inhibition of kidney TrxR, while in liver a significant inhibition was observed after exposure to 5 and 10 mg/Kg of MeHg (TrxR was determined 24 hours after MeHg). In brain, MeHg did not inhibit TrxR. In vitro results demonstrated that MeHg inhibited brain (0.05 1 μM) , liver (0.05 1 μM) and kidney (0.025 1 μM) TrxR in a dose dependent manner Here, we have extended the characterization of mechanisms associated with the neuroprotective effects of flavonoids quercetin and quercitrin against MeHg-induced toxicity. In addition, we provided novel data establishing that (1) calcium plays a central role in MeHg toxicity, (2) in brain slices MeHg induces mitochondrial oxidative stress both via direct interaction with mitochondria as well as via mitochondria- indirect mechanisms. In addition (3) MeHg (5mg/kg) caused a number of behavioural alterations that are related with an inhibition of cerebelar and cerebral GPx and Na+/K+ ATPase activities and (4) increased in lipid peroxidation.The higly affinity of MeHg to selenol groups of endogenous molecules can lead to (5) inhibition of thioredoxin reductase that can contribute to MeHg toxicity. We conclude that MeHg lead to increase in mitochondria ROS generation that contributes to increase in lipid peroxidation. In addition, the inhibition of important antioxidant enzymes such as GPx ans TrxR can contribute to oxidative damage that can be related to development of behavioral damage. In this view the antioxidant activity of flavonoids quercetin and quercitrin seems to be direct associate with the capacity of flavonoids to confere protection against MeHg toxicity. O metilmercúrio (MeHg) é um importante agente tóxico ambiental que pode causar desordens neurocomportamentais e neurofisiológicas irreversíveis em humanos e animais experimentais. Os principais mecanismos pelos quais o MeHg induz toxicidade são: a ruptura na homeostase do cálcio intracelular, a indução de estresse oxidativo, a inibição da atividade da Na+/K+ ATPase neuronal e mudanças nos níveis das enzimas antioxidantes. Adicionalmente, dados recentes relatam o envolvimento do sistema da tiorredoxina como um dos alvos de toxicidade do MeHg. Por outro lado, os flavonóides possuem propriedades quelantes para metal divalente, atividade antioxidante e são permeáveis a barreira cérebro-sangue. Além disso, eles podem oferecer neuroproteção a uma variedade de modelos animais e celulares de doenças neurológicas, incluindo proteção contra a toxicidade do MeHg. Considerando que o exato mecanismo pelo qual o MeHg exerce toxicidade permanece desconhecido e que poucos e controversos dados sobre a interação do MeHg com flavonóides são encontrados na literatura, este estudo avaliou os mecanismos de toxicidade do MeHg em modelos in vitro e in vivo bem como, o desempenho de diferentes flavonóides: quercetina, quercitrina e rutina em diferentes modelos de toxicidade induzidos pelo MeHg. Nosso estudo mostrou que o MeHg (100μM) causou aumento na peroxidação lipídica e na produção de espécies reativas de oxigênio (EROs) em fatias de córtex de ratos. Os flavonóides quercitrina (25 μg/mL) e quercetina (5, 10 e 25 μg/mL) protegeram contra esta toxicidade, e contra o aumento de ERO produzidas pelo MeHg (5μM) nas mitocôndrias. Diferentemente, o flavonóide rutina não obteve efeito protetor contra a indução da peroxidação lipídica e produção de ERO induzidas pelo MeHg em fatias corticais de cérebro. O aumento na produção de ERO, geradas pelo MeHg, foi dependente do aumento dos níveis intracelulares de cálcio (artigo 1). Já, estudos in vivo com camundongos tratados oralmente com MeHg (5mg/kg), durante 30 dias, mostraram um marcado aumento nos parâmetros de toxicidade (diminuição no ganho de peso, aumento na freqüência de micronúcleos e nefrotoxicidade), diminuição no desempenho do sistema motor (atividade locomotora e coordenação motora), e deficiência na memória espacial, bem como alterações em vários parâmetros bioquímicos (diminuição na atividade da glutationa peroxidase (GPx) e Na+/K+ ATPase e aumento na peroxidação lipídica). O co-tratamento com quercitrina (10mg/kg) pela via intraperitoneal, diminuiu as alterações comportamentais principalmente por diminuir os níveis de peroxidação lipídica e manter a atividade da GPx e da Na+/K+ ATPase iguais aos níveis do controle (manuscrito 1). Além disso, nosso estudo demonstrou, pela primeira vez, que o MeHg inibe a atividade da tiorredoxina redutase (TrxR). Uma única administração oral de MeHg (1, 5, 10 mg/kg), causou uma marcada inibição na atividade da TrxR renal, enquanto no fígad observou-se uma inibição significativa após exposição a 5 e 10 mg/kg (a atividade da TrxR foi determinada 24 horas após a administração de MeHg). No cérebro, o MeHg não inibiu a atividade da TrxR in vivo (artigo 2). Já os resultados in vitro revelaram que o MeHg causou uma inibição concentração dependente na atividade da enzima TrxR isolada de cérebro (0,05 1 μM) fígado (0,05 - 1 μM) e rim (0,025 1 μM). Assim, nós ampliamos a caracterização dos mecanismos associados com os efeitos neuroprotetores dos flavonóides quercetina e quercitrina na toxicidade induzida pelo MeHg. Adicionalmente, outros dados sobre a toxicidade do MeHg, foram obtidos, tais como: (1) o cálcio desempenha um papel central na toxicidade do MeHg, (2) em fatias de cérebro de ratos o MeHg induz estresse oxidativo mitocondrial via interação direta com as mitocôndrias, bem como via mecanismos mitocondriais indiretos. Além disso, (3) o MeHg (5mg/kg) pode levar a inúmeras alterações comportamentais que podem estar relacionadas à inibição da atividade das enzimas GPx e Na+/K+ ATPase e (4) aumento na peroxidação lipídica. A alta afinidade do MeHg por grupos selenóis das moléculas endógenas pode levar (5) a inibição da TrxR o que pode contribuir para a toxicidade do MeHg. Podemos concluir que o MeHg leva a um aumento na produção de ERO pelas mitocôndrias, o que contribui para um aumento na peroxidação lipídica induzida pelo MeHg. Além disso, a inibição de importantes enzimas antioxidantes como a GPx e a TrxR podem contribuir para aumentar o dano oxidativo, que parece estar relacionado com o aparecimento dedanos comportamentais. Desta forma a atividade antioxidante dos flavonóides quercetina e quercitrina parece estar diretamente associada à capacidade destes compostos emproteger contra a toxicidade do MeHg.
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- 2010
41. Hepato and neuroprotective activities of diethyl-2-phenyl-2-tellurophenyl vinylphosphonate
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Ávila, Daiana Silva de, Soares, Félix Alexandre Antunes, Rocha, João Batista Teixeira da, Farina, Marcelo, and Puntel, Robson Luiz
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Glutamato ,Manganese ,Neuroprotetor ,Telúrio ,Acetaminofeno ,Neuroprotector ,Hepatoprotetor ,Antioxidante ,Manganês ,Tellurium ,Glutamate ,Antioxidant ,Hepatoprotector ,CIENCIAS BIOLOGICAS::BIOQUIMICA [CNPQ] ,Acetaminophen - Abstract
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Despite the growing use of organotellurium compounds in the chemistry and biochemistry field, little is known about the pharmacology of these compounds. The diethyl-2-phenyl-2-tellurophenyl vinylphosphonate (DPTVP) is a vinylic telluride wich shows low toxicity in mice and a high antioxidant activity in vitro. These previous data encoraged us to evaluate the antioxidant potential and the pharmacological benefits that the compound could provide. It was observed that the compound can protect at low concentrations (from 1μM) against the increased lipid peroxidation in brain induced by the neurotoxic agents sodium nitropruside (SNP) and quinolinic acid (QA) in vitro. Furthermore, DPTVP also protected against the mitochondrial dysfunction induced by SNP in cortex, hippocampus and striatum of rats. Besides, the compound did not show neurotoxic effect, once it did not altered mitochondrial viability and neither the glutamatergic system in vitro at the antioxidant concentrations (until 50μM). Considering the possible neuroprotective effect of DPTVP in vitro, the model of Mn neurotoxicity in rats was used in order to evaluate it in vivo and ex vivo. The exposure to Mn for 4 months (137mg/Kg) caused an impairment of the exploratory and motor activity of the rats, as well as alterations in the biochemical parameter analyzed, such as increase in the lipid peroxidation and reduction in the mitochondrial viability and in the [3H] glutamate uptake in striatum, allied to increase in the Mn levels in this brain structure. The treatment for two weeks with DPTVP partially recoved from the neurobehavioral alterations, probably due to the protective effect against the oxidative damage caused by Mn in the striatum observed post mortem. Nevertheless, the animals treated with DPTVP did not showed increased levels of Mn in their striatum, indicating that the compound can act not only as an antioxidant against manganism, but can also impairs the influx or facilitates Mn efflux in thia area. The hepatoprotective activity of DPTVP was also verified against the acetaminophen (APAP) in mice. Both APAP does (200 and 300mg/Kg) caused hepatic alterations sucs as non-proteic SH depletion, Increase in TBARS levels, inhibition of δ- ALA D, ALT leakage and morphologic damage to the hepatocytes, nevertheless at different intensities. Hence, The treatment with DPTVP (30, 50 and 100μmol/Kg) showed effectiveness when the APAP dose preadministeres was 200mg/Kg. Against the dose of 300mg/Kg, the compound has just recovered from the histomorphologic alterations to hepatocytes. The present estudy has also evidenced that the antioxidant activity depicted by the vinilc telluride is due to its scavenger activity, once the compound was able to neutralize reative oxygen (ROS) and reactive nitrogen species (RNS), such as H2O2, OH , ON and ONOO-, probably due to the formation of telluroxide, which is due to the molecular structure of the compound. Taken together, these results suggest that DPTVP has neuro and hepatoprotective actions at low doses probably due to its strong antioxidant activity and that the formation of telluroxide is very important to these effects. Apesar do crescente uso dos compostos orgânicos de telúrio na química e na bioquímica, pouco se sabe sobre a farmacologia de tais compostos. O Dietil-2- fenil-2-telurofenil vinilfosfonato (DPTVP) é um telureto vinílico que apresenta baixa toxicidade em camundongos e uma elevada atividade antioxidante in vitro. Estes dados prévios da literatura nos encorajaram a avaliar mais a fundo esse potencial antioxidante e os benefícios farmacológicos que o composto poderia proporcionar. Foi verificado que o composto protege contra o aumento na peroxidação lipídica em cérebro induzida por agentes neurotóxicos como o ácido quinolínico (QA) e o nitroprussiato de sódio (SNP) in vitro em baixas concentrações (a partir de 1μM). O DPTVP também protegeu contra a disfunção mitocondrial induzida por SNP em córtex, hipocampo e estriado de ratos. Além disso, o composto demonstrou baixa neurotoxicidade, uma vez que não alterou a viabilidade mitocondrial nem o sistema glutamatérgico in vitro nas concentrações antioxidantes (até 50μM). Diante da possível atividade neurotoprotetora observada in vitro pelo DPTVP, o modelo de neurotoxicidade induzido por Mn foi utilizado a fim de avaliá-lo in vivo e ex vivo. A exposição ao Mn por 4 meses (137mg/Kg) causou um prejuízo à atividade exploratória e motora dos ratos, bem como alterações em parâmetros bioquímicos analizados como aumento na lipoperoxidação, redução da viabilidade mitocondrial e redução na captação de [3H]glutamato no estriado, aliado ao aumento nos níveis do metal nessa estrutura. O tratamento por duas semanas com o DPTVP recuperou parcialmente as alterações neurocomportamentais devido à reversão dos danos oxidativos causados pelo Mn no estriado observados post mortem. Além disso, os animais tratados com o DPTVP não demonstraram níveis elevados de Mn no estriado, indicando que o composto pode alterar as condições de transporte do Mn nesse area. Também foi verificada a atividade hepatoprotetora do DPTVP contra o acetaminofeno (APAP) em camundongos. Ambas as doses (200 e 300mg/Kg de APAP) causaram alterações hepáticas como depleção de SH não-protéico, aumento nos níveis de TBARS, inibição da δ-ALA-D, extravazamento de ALT para o sangue e danos morfológicos aos hepatócitos, entretanto em diferentes intensidades. Dessa maneira, o tratamento com DPTVP (30, 50 e 100μmol/Kg) foi bastante efetivo quando a dose de APAP foi a de 200mg/Kg. Já na dose de 300mg/Kg de APAP, o composto apenas recuperou de fato as alterações histomorfológicas dos hepatócitos. O presente trabalho também evidenciou que a atividade antioxidante do telureto vinílico provavelmente deve-se à sua atividade neutralizadora ou scavenger , uma vez que o composto mostrou-se efetivo em capturar tanto espécies reativas de oxigênio (ERO) quanto de nitrogênio (ERN), como o H2O2, o OH , ON e o ONOO-, provavelmente devido à formação de teluróxido favorecida pela estrurura do composto. Esses resultados sugerem que o DPTVP possui ações hepato e neuroprotetoras em baixas doses devido ao seu potencial antioxidante, e que a formação de teluróxido seja essencial para esses efeitos.
- Published
- 2009
42. Analysis of the antioxidant properties of the 3-(phenyl hydrazone) butane-2-one and butane-2,3-Dionethiosemicarbazone oximes
- Author
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Puntel, Gustavo Orione, Soares, Félix Alexandre Antunes, Rocha, João Batista Teixeira da, Schetinger, Maria Rosa Chitolina, and Barbosa, Nilda Berenice de Vargas
- Subjects
Reactive species ,Butane-2,3-dionethiosemicarbazone oxime ,Antioxidante ,Oxima butana-2,3- dionatiosemicarbazona ,Antioxidant ,Espécies reativas ,CIENCIAS BIOLOGICAS::BIOQUIMICA [CNPQ] ,3-(phenylhydrazono)butan-2-one oxime ,Oxima 3-(fenil hidrazona) butano-2-ona - Abstract
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Oximes are chemical compounds used to reactivate the inhibited acetylcholinesterase (AChE) enzyme by organophosphates (OPs). The OPs, besides classically recognized as AChE irreversible inhibitors, are also involved in the generation of oxidative stress conditions. However, researches focusing on the possible antioxidant properties of oximes are lacking in the literature. The aim of this study was to investigate the potential antioxidant and toxic properties of 3-(phenylhydrazono)butan-2-one oxime and butane-2,3-dionethiosemicarbazone oxime in mice, and to understand the mechanism(s) by which they act. Firstly, we investigated the existence and the mechanism(s) by which 3- (phenylhydrazono)butan-2-one oxime exert its antioxidant properties (Manuscript 1). The obtained results show that in vitro hydrogen peroxide (H2O2), malonate, or ferrous ions (Fe2+)-induced lipid peroxidation was decreased by low concentrations of the oxime. Oxime treatment did not modify the basal peroxidation level nor prevented the induced lipid peroxidation determined ex vivo. The obtained results suggest that 3-(phenylhydrazono)butan-2-one oxime could be employed as a satisfactory antioxidant compound. The absence of toxicity signs after in vivo administration of 3-(phenylhydrazono)butan-2-one oxime to mice may indicate that it could be a safe drug for further studies. The other objective of this study was to investigate the existence and the mechanism(s) by which butane-2,3-dionethiosemicarbazone oxime exert its antioxidant properties (Manuscript 2). The obtained results indicate a significant H2O2, nitric oxide (NO) and 1,1-diphenyl-2-picrylhydrazyl (DPPH●) scavenging activity at low oxime concentrations. Besides, the butane-2,3-dionethiosemicarbazone oxime significantly diminished the deoxyribose degradation induced by Fe2+ or Fe2+ + H2O2, and also the benzoate hydroxylation induced by ferric ions (Fe3+) + H2O2 reaction. Besides, the oxime showed a significant inhibitory effect on s-phenantroline reaction with Fe2+. A significant decrease in the basal and pro-oxidants induced lipid peroxidation in brain, liver, and kidney of mice was observed both in vitro and ex vivo. In addition, in our ex vivo experiments the butane-2,3- dionethiosemicarbazone oxime did not determine significant changes in thiol (-SH) levels of liver, kidney and brain, as well as did not modify the delta-aminolevulinate dehydratase (δ- ALA-D) activity in these tissues of mice. The obtained results indicate that the oximes tested depicted significant antioxidant properties, and that further studies are necessary to improve our knowledge regarding the exact antioxidant action mechanism of these oximes. As oximas são compostos químicos utilizados para reativar a enzima actilcolinesterase (AChE) inibida por organofosforados (OPs). Os OPs, além de serem classicamente reconhecidos como inibidores da AChE, também estão envolvidos em situações que geram estresse oxidativo. Contudo, pesquisas enfocando as possíveis propriedades antioxidantes das oximas são escassas na literatura. O objetivo deste estudo foi investigar o potencial antioxidante e as propriedades tóxicas das oximas 3-(fenil hidrazona) butano-2-ona e butana- 2,3-dionatiosemicarbazona em camundongos, e entender o(s) possível(is) mecanismo(s) pelo(s) qual(is) elas atuam. Inicialmente investigamos a existência, e o(s) mecanismo(s) pelo(s) qual(is) a oxima 3-(fenil hidrazona) butano-2-ona exerce suas propriedades antioxidantes (Manuscrito 1). Os resultados obtidos mostram que a peroxidação lipídica induzida por peróxido de hidrogênio (H2O2), por malonato, e por íons ferrosos (Fe2+) foi diminuída em baixas concentrações da oxima. O tratamento dos camundongos com a oxima não alterou os níveis basais de peroxidação lipídica, nem preveniu a peroxidação lipídica induzida em experimentos ex vivo. Os resultados obtidos sugerem que a oxima 3-(fenil hidrazona) butano-2-ona pode ser empregada como um satisfatório composto antioxidante. A ausência de sinais de toxicidade após a administração in vivo da oxima 3-(fenil hidrazona) butano-2-ona em camundongos indica que esta pode ser uma droga segura para futuros estudos. O outro objetivo deste estudo foi investigar a existência e o(s) mecanismo(s) pelo(s) qual(is) a oxima butana-2,3-dionatiosemicarbazona exerce suas propriedades antioxidantes (Manuscrito 2). Os resultados obtidos indicam uma significativa atividade da oxima em neutralizar H2O2, o radical 1,1-difenil-2-picrilhidrazil (DPPH●), e a formação de óxido nítrico (NO), em baixas concentrações. Além disso, a oxima butana-2,3-dionatiosemicarbazona diminuiu significativamente a degradação da desoxirribose induzida por Fe2+ e pela reação Fe2+ + H2O2, e também a hidroxilação do benzoato induzida pela reação íons férricos (Fe3+) + H2O2. Além disso, a oxima apresentou um efeito inibitório significativo na reação da s- fenantrolina com Fe2+ Uma diminuição significativa na peroxidação lipídica basal e na peroxidação lipídica induzida por agentes pro-oxidantes no cérebro, fígado e rim de camundongos foi observada tanto in vitro quanto ex vivo. A oxima butana-2,3- dionatiosemicarbazona não determinou mudanças nos níveis de tióis (-SH) no fígado, rim e cérebro, bem como não modificou a atividade da enzima delta-aminolevulinato desidratase (δ-ALA-D) nestes tecidos de camundongos em experimentos ex vivo. Os resultados obtidos indicam que as oximas testadas apresentaram propriedades antioxidantes significativas, e que futuros estudos são necessários para aumentar o conhecimento a respeito do exato mecanismo de ação antioxidante destas oximas.
- Published
- 2008
43. Antioxidant activity of (e)-1-(1-(methylthio)-1-selenopheny) hept-1-en-2-yl) pyrrolidin-2-one: an organoselenium compound with low toxicity
- Author
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Ineu, Rafael Porto, Zeni, Gilson Rogério, Rocha, João Batista Teixeira da, Folmer, Vanderlei, and Rodrigues, Oscar Endrigo Dorneles
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Selenium ,Organoselênio ,Toxicity ,Espécies reativas de oxigênio ,Oxidative stress ,Estresse oxidativo ,Organoselenium ,Antioxidante ,Fluorescência ,Toxicidade ,Antioxidant ,Reactive oxygen species ,CIENCIAS BIOLOGICAS::BIOQUIMICA [CNPQ] - Abstract
Conselho Nacional de Desenvolvimento Científico e Tecnológico The objective of this work was to evaluate the antioxidant activity of (E)-1-(1-(methylthio)-1-selenopheny) hept-1-en-2-yl) pyrrolidin-2-one: an organoselenium compound with low toxicity (compound 1). A number of parameters were examined in brain, liver and plasma of rats and mice as indicators of toxicity, including reactive species to the thiobarbituric acid levels, ascorbic acid content, δ-aminolevulinate dehydratase and catalase activity, AST, ALT, urea and creatinine levels. Ours experiments demonstrated that in vitro, compound 1 showed a concentration-dependent reduction in TBARS production and in the generation of reactive species (RS) caused by Fe2+/malonate when was tested by DCFH-DA oxidation. The LD50 for compound 1 was calculated administering by oral route and the results demonstrated higher than 500 mg/kg. We also examined the toxicity of the compound 1 in ex vivo experiments and the results demonstrated that it did not change hepatic δ-aminolevulinate dehydratase activity at 100 and 250 mg/kg only showed an inhibition at the highest dose (500mg/kg) of compound 1 but in this same dosage no significant differences were detected in brain of mice. Hepatic lipid peroxidation in treated mice did not differ from control values otherwise, in brain tissue, all doses showed a significant reduction in TBARS levels. One of the biochemicals parameters measured were urea and creatinine levels in plasma of treated mice treated. The urea levels showed a decrease at highest dose and creatinine to increase at middle and high doses. Ascorbic acid content, that is an endogenous antioxidant, was increased only at the highest dose of compound 1. Catalase activity in brain of exposed mice had a tendency to decrease and showed a significant result only at 100mg/kg. In contrast with this, in hepatic tissue, the catalase activity showed a significant increased in all doses. We concluded that this is a promising compound with greater antioxidant activity and low toxicity but are necessary many detailed pharmacological studies involving this type of organoselenium compounds. O objetivo desse trabalho foi avaliar a atividade antioxidante do E-1,1-metiltioselenofenil-2-pirrolidinona-hepteno (composto 1); um composto orgânico de selênio que apresenta baixa toxicidade. Um grande número de parâmetros foram avaliados em cérebro, fígado e plasma de ratos e camundongos e foram usados como indicadores de toxicidade: níveis de TBARS e ácido ascórbico, atividade da δ-ALA-D e da catalase, e níveis de ALT, AST, uréia e creatinina. Nossos experimentos demonstraram que, in vitro, o composto 1 apresentou uma redução dependente da concentração na produção de TBARS e na geração de espécies reativas (RS) induzidos por Fe2+/malonato quando o teste utilizado foi o da oxidação da DCFH-DA. A dose letal (LD50) para o composto 1 foi calculada quando administrada pela via oral e os resultados demonstraram ser esta maior do que 500 mg/kg. Utilizando experimentos ex vivo medimos a toxicidade do composto 1 e os resultados demonstraram que esse composto não mudou a atividade da δ-ALA-D (delta-aminolevulinato desidratase) em 100 e 250 mg/kg e que somente apresentou uma inibição da atividade na maior dose (500mg/kg) entretanto, nessa mesma dose não houve nenhuma diferença significante na atividade da δ-ALA-D em cérebros de camundongos. A peroxidação lipídica em tecidos hepáticos de camundongos não foi alterada comparando-a com o grupo controle contudo, em tecido cerebral todas as doses testadas apresentaram uma redução significante nos níveis de TBARS. Os níveis de uréia diminuíram somente na maior dose, já os de creatinina aumentaram em doses média e alta. Também foram avaliados os níveis de ácido ascórbico e apresentaram aumentados somente na maior dose. No cérebro de camundongos, a atividade da catalase diminuiu significantemente em 100mg/kg. Em oposição a isso, no tecido hepático a atividade da catalase apresentou um aumento significante em todas as doses. Com esses resultados, nós concluímos que trata-se de um composto promissor que apresenta uma grande atividade antioxidante e uma baixa toxicidade, entretanto são necessários mais estudos farmacológicos detalhados.
- Published
- 2007
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