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The purpose of this work was the development of an alternative ocular tetrahydrozoline hydrochloride (THZ) microemulsion for the management of allergic conjunctivitis. Pseudo-ternary phase diagrams were used to produce the microemulsions. For the formulation of the microemulsions, isopropyl myristate was selected as oil. Furthermore, various surfactants were applied for the determination of their suitability; ME-1 and ME-4 were developed using Sorbitan monolaurate 80 and Polysorbate 80, for ME-2 and ME-5 Sorbitan monolaurate 80 and macrogolglycerol ricinoleate while for ME-3 and ME-6 Sorbitan monolaurate 80 and Polysorbate 20. For ME-1, ME-2, and ME-3 propylene glycol and ethanol, for ME-4, ME-5, and ME-6 ethanol and polyethylene glycol were used as co-surfactants. Various characterization parameters of microemulsions were evaluated such as droplet size, conductivity, zeta potential, viscosity, and pH. In addition, the drug release, stability, sterility, safety, ex vivo, and in vivo experiments were studied. The characterization showed that the formulations can act as suitable carriers for eye application. In addition, it was revealed that microemulsions were found stable and sterile. The formulations released the drug in a sustained manner. Ex vivo diffusion studies exhibited that the microemulsions can be used for topical delivery to the eye. Assessment of in vitro ocular irritation was conducted by an in vivo prediction model, EpiOcular™ eye irritation test. Based on the in vivo studies, the chosen ideal microemulsion showed longer contact time to the cornea than the commercial product. Moreover, the developed ocular carrier was found to be safe from the viewpoint of in vitro ocular irritancy and mutagenicity. In conclusion, according to characterization results, the THZ microemulsions can act as a hopeful approach for topical eye application.

Abstract: Some novel triazole-bearing ketone and oxime derivatives were synthesized from Ibuprofen. In vitro cytotoxic activities of all synthesized molecules against five cancer lines (human breast cancer MCF-7, human lung cancer A549, human prostate cancer PC-3, human cervix cancer HeLa, and human chronic myelogenous leukemia K562 cell lines) were evaluated by MTT assay. In addition, mouse embryonic fibroblast cells (NIH/3T3) were also evaluated to determine the selectivity. Compounds 18, 36, and 45 were found to be the most cytotoxic, and their IC50 values were in the range of 17.46–68.76 µM, against the tested cancer cells. According to the results, compounds 7 and 13 demonstrated good anti-inflammatory activity against the microsomal enzyme prostaglandin E2 synthase-1 (mPGES-1) enzyme at IC50 values of 13.6 and 4.95 µM. The low cytotoxicity and non-mutagenity of these compounds were found interesting. Also, these compounds significantly prevented tube formation in angiogenesis studies. In conclusion, the anti-inflammatory and angiogenesis inhibitory activities of these compounds without toxicity suggested that they may be promising agents in anti-inflammatory treatment and they may be supportive agents for the cancer treatment. Graphical abstract: [Figure not available: see fulltext.].

The pivotal role of the myeloid ecotropic viral integration site 1 (MEIS1) transcriptional factor was reported in cardiac regeneration and hematopoietic stem-cell (HSC) regulation with our previous findings. MEIS1 as a promising target in the context of pharmacological inhibition, we identified a potent myeloid ecotropic viral integration site (MEIS) inhibitor, MEISi-1, to induce murine and human HSC expansion ex vivo and in vivo. In this work, we performed lead optimization on MEISi-1 by synthesizing 45 novel analogues. Structure-activity relationship studies revealed the significance of a para-methoxy group on ring A and a hydrophobic moiety at the meta position of ring B. Obtained biological data were supported by inhibitor docking and molecular dynamics simulation studies. Eleven compounds were depicted as potent inhibitors demonstrating a better inhibitory profile on MEIS1 and target genes Meis1, Hif-1 alpha, and p21. Among those, 4h, 4f, and 4b were the most potent inhibitors. The predicted pharmacokinetics properties fulfill drug-likeness criteria. In addition, compounds exerted neither cytotoxicity on human dermal fibroblasts nor mutagenicity.

Nanotechnology-based drugs show superiority over conventional medicines because of increased bioavailability, lower accumulation in non-target tissues, and improved therapeutic index with increased accumulation at target sites. However, it is important to be aware of possible problems related to the toxicity of these products, which have therapeutically superior properties. Accordingly, the present study was designed to investigate the safety profile of amoxicillin nanoparticles (AmxNPs) that we developed to increase the oral bioavailability of amoxicillin (Amx) in poultry. In the first part of the study, the genotoxicity potential of AmxNPs was evaluated using the Ames test and the in vitro comet assay. The results of Ames test showed that none of the tested concentrations of Amx and AmxNPs cause a significant increase in the revertant number of Salmonella typhimurium strains TA98, and TA100, either with or without metabolic activation. Similarly, the comet assay revealed that AmxNPs did not induce DNA damage at any of the concentrations used, whereas high-dose (200 μg/mL) of Amx caused a significant increase in the percentage of DNA in the tail. In the second part of the study, the toxicity potential of AmxNPs on broilers was investigated by measuring biochemical parameters. In vivo results demonstrated that AmxNps did not cause a significant change in biochemical parameters, whereas Amx increased ALT, glucose, and cholesterol levels at certain sampling times. The obtained findings suggest that AmxNPs could be a safe promising potential drug in drug delivery systems.

Aging and diseases related to aging, such as cancer, have been linked to oxidative stress. On the other hand, calorie restriction (CR) is one of the most effective interventions to slow down aging and prevent a variety of diseases such as cancer in preclinical models. CR has also been reported to modify oxidative stress. The aim of this study was to investigate the effects of different CR protocols and aging on oxidative stress parameters in the MMTV-TGF-α breast cancer mouse model in a cross-sectional study. Female mice were randomly enrolled in three groups: ad libitum (AL), chronic calorie restriction (CCR, 15% CR) or intermittent calorie restriction (ICR, three weeks AL followed by one week 60% CR in cyclic periods) starting at the age of 10 weeks until 81/82 weeks of age. Liver samples were analyzed for malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GSH-Px) levels. At week 49/50, the GSH level increased significantly in the CCR group compared to the AL and ICR-R groups which had higher mammary tumor (MT) incidence rates. Additionally, liver MDA levels in ICR groups were significantly increased, while aging led to decreased CAT and SOD activities in all CR groups. The application of different CR protocols did not have any significant effect on MDA, CAT, and SOD parameters in the liver at week 81/82. These results suggest that although GSH may interfere with MT development at the systemic level, many of the oxidative stress parameters may have more local effects on tumor development than the systemic effects.

In this study, the level of arsenic (As), lead (Pb) and cadmium (Cd) and also essential elements in beer samples consumed in Turkey were investigated using the inductively coupled plasma mass spectrometry (ICP-MS) method. The heavy metal-induced non-carcinogenic and carcinogenic risks were calculated. For essential elements, the calculated estimated daily intake of iron (Fe), copper (Cu), selenium (Se) and cobalt (Co) from beer consumption were compared with their toxicity reference values. Tukey post-hoc test showed that As was found at a significantly higher level when compared to Pb. Also, a significant correlation was found between As level and alcohol by volume percent. All samples had a hazard quotient and hazard index

Calorie restriction (CR) is one of the most effective methods to prevent many diseases including cancer in preclinical models. However, the molecular mechanism of how CR prevents cancer is unclear. The aim of this study was to understand the role of oxidative stress (OS) in the preventive effects of different types of CR in aging mouse mammary tumor virus-transforming growth factor-alpha (MMTV-TGF-alpha) female mice. Mice were enrolled in ad libitum (AL), chronic CR (CCR, 15% CR) or intermittent CR [ICR, 3 weeks AL (ICR-Refeed, ICR-RF) and 1 week 60% CR (ICR-Restriction, ICR-R) in cyclic periods] groups started at the age of 10 weeks and continued until 81/82 weeks of age. Blood samples were collected to measure malondialdehyde (MDA), glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) levels. There was no significant difference for MDA levels among the dietary groups although the chronic calorie restriction (CCR) group had lower MDA levels compared to intermittent calorie restriction (ICR) and AL group at different time points. There was also no change in MDA levels of CCR group with aging. On the other hand, the CCR group had higher CAT and SOD activity compared to ICR-R, ICR-RF, and AL groups. Moreover, GSH level was higher in CCR compared to ICR group at week 49/50 (p < .05). CAT and SOD activities were also positively correlated (p < .05). Here, for the first time, the long-term (72 weeks) effects of different types of CR on OS parameters were reported. In conclusion, moderate that is, 15%, CCR is more likely to be protective compared to the same overall calorie deficit implemented by ICR against OS that may play role in the preventive effects of CR.

In recent years, the hydrophobic active substances have led researchers to develop new formulations to enhance bioavailability and dissolution rate; brinzolamide, a lipophilic drug belongs to carbonic anhydrase inhibitors, which cause reduction of intraocular pressure in patients suffering from glaucoma. Currently, the marketed product of brinzolamide is in the form of ocular drops; nonetheless, the conventional drops provide decreased therapeutic efficacy owing to their low bioavailability and pulsed drug release. Thus, the development of novel ocular formulations such as topical microemulsions is of high importance. In this work, the preparation of new microemulsions containing brinzolamide (0.2, 0.5 and 1% w/w) and comprised from isopropyl myristate, tween 80 and span 20 and Cremophor EL was performed. The obtained microemulsions were further characterized for their physicochemical properties. In addition, Fourier Transformed-Infrared spectroscopy was used touate the compatibility of active ingredients and components. In vitro release studies along with kinetic modeling were performed using the dialysis membrane method in simulated tear fluid. Bioadhesion studies were performed using Texture analysis. Finally, in vitro ocular irritation based on EpiOcular™ Eye Irritation Test and cytocompatibility studies was performed to examine any possible harm on ocular cells and predict in vivo safety profile.

Breastfeeding is considered a gold standard for infant development. However, several complications such as nipple fissure, infection and ulceration might be accomplished during nursing, which may lead to early cessation of breastfeeding. For this purpose, silver-made nipple cap SilverNurse (R) (SN) has been designed to control symptoms of nipple fissure in lactating women by aiming to eliminate antimicrobial resistance compared to the alternative treatment methods. Therefore, aim of the present study is to assess antimicrobial efficacy and dermal safety of silver-made SN in context of biocompatibility with cytotoxicity assay, in vitro EpiDetin skin irritation and in vivo skin irritation tests. According to the represented results, SN exhibited potent antimicrobial activity on Staphylococcus aureus, Escherichia soli, Enterococcus hirae, and Pseudonionas aeruginosa bacteria as well as Candida albicans fungi. Cytotoxicity by MTT assay showed that prepared extract of SN has a lack of cytotoxicity in tested concentrations. In addition, in vitro EpiDerm skin irritation model and in vivo skin test demonstrated that SN can be classified as biocompatible and non-irritant for dermal use without any sign of erythema and edema. Therefore, in the present study, it was evaluated that SN can be applied safely in daily comfort fields for lactating women without dermal complications related to infection and skin irritation.

Over the last decade, electrolyzed water (EW) produced by salt and tap water has gained importance due to its antimicrobial effects. Regarding to chlorine-based compounds, EW also used in post-harvest safety of food processing and sterilization of surfaces. The latest studies suggested that EW might act as wound healing agent due to anti-infective and cell proliferative properties. In this study, we evaluated acute contact cytotoxicity in L929 mice fibroblast cells and wound healing activity of EWsin vitro.In addition, mutagenic activity was evaluated by Ames test with and without metabolic activation by S9 fraction and the stability profile of freshly prepared EWs has been followed up. According to the results, strong acid (StAEW) and mixed EW (MEW) showed dose-dependent cytotoxicity due to possible high HOCl concentration, while slightly acidic and catholyte EW (CEW) were not cytotoxic even applied directly for 30 sec. Further, StAEW and CEW showed a significant increase in L929 cell migration in scratch assay. Likewise, with/ without metabolic activation, neither of EWs had shown mutagenic profile in TA 98 and TA100 strains ofSalmonella typhimurium.Follow-up of ORP (oxidation-reduction potential), pH and FCC (free chlorine concentration) showed that temperature and light were important storage conditions to maintain a stable profile particularly for ORP and FCC, which are the most important indicators for biological activity of EW. According to the present findings, it can be suggested that particularly StAEW, may represent a valuable wound healing agent with an achievable, economical and easy production system when stored under proper conditions. TUBITAK (Turkish Research and Scientific Council)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [116Z169] The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This project was financially supported by TUBITAK (Turkish Research and Scientific Council) 1002 program with a Grant No. 116Z169. The authors also thank to Gulenay Alyurt for her considerate effort on EW project. WOS:000568535700001 2-s2.0-85090558478 PubMed: 32909829

The antioxidant and mutagenic/antimutagenic activities of the fixed oils from Nigella sativa (NSO) and Nigella damascena (NDO) seeds, obtained by cold press-extraction from the cultivar samples, were comparatively investigated for the first time. The antimutagenicity test was carried out using classical and modified Ames tests. The fatty acid composition of the fixed oils was characterized by gas chromatography-mass spectrometry (GC-MS) while the quantification of thymoquinone in the fixed oils was determined by UPC2 . The main components of the NSO and NDO were found to be linoleic acid, oleic acid, and palmitic acid. The results of the Ames test confirmed the safety of NSO and NDO from the viewpoint of mutagenicity. The results of the three antioxidant test methods were correlated with each other, indicating NDO as having a superior antioxidant activity, when compared to the NSO. Both NSO and NDO exhibited a significant protective effect against the mutagenicity induced by aflatoxin B1 in Salmonella typhimurium TA98 and TA100 strains. When microsomal metabolism was terminated after metabolic activation of the mycotoxin, a significant increase in antimutagenic activity was observed, suggesting that the degradation of aflatoxin B1 epoxides by these oils may be a possible antimutagenic mechanism. It is worthy to note that this is the first study to assess the mutagenicity of NSO and NDO according to the OECD 471 guideline and to investigate antimutagenicity of NDO in comparison to NSO against aflatoxin.

This study aimed to obtain necessary toxicological data using experimental and computational methods for the calculation of a common permitted daily exposure (PDE) which can be relevant for nicotinic acid and its esters and nicotinamide according to European Medicines Agency Guideline on setting health-based exposure limits. PDE calculation is mainly based on critical toxicological endpoints. During this procedure, critical toxicological endpoints data of an active pharmaceutical ingredient (API) may not be able to find satisfactorily. Hence, using toxicological data for another API that has a similar chemical structure can be a useful way. In this study, toxicological endpoints of nicotinic acid and its esters and nicotinamide were evaluated. Then, the data gaps in the toxicological endpoints were filledusing the read-across approach. Based on the current existing data, nicotinic acid and its esters and also nicotinamide are not genotoxic and do not have skin sensitization potential. These compounds do not present a concern for carcinogenicity and developmental/reproductive toxicity. Based on these critical endpoints and available experimental data, the final PDE of 10 mg/day was calculated for all category members. Our study showed the utility of the read-across for PDE calculation of APIs with experimental toxicological data gap. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s43188-020-00069-8) contains supplementary material, which is available to authorized users.

Energy drinks (ED) are containing large doses of metabolic stimulants and its use with ethanol has increased dramatically among young adults. In this study, we examined the effects of ED exposure either alone or in combination with ethanol on oxidative stress parameters including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and lipid peroxidation parameter malondialdehyde (MDA) in rat. Some histopathological findings were also evaluated. ED exposure led to a dose-dependent increase in liver MDA compared to the control indicating oxidative damage. Histopathological findings also revealed that ED alone may generate liver damage. Ethanol exposure increased MDA level and SOD, CAT, and GSH-Px activity in both the brain and the liver. The combination of ethanol and ED produced greater damage which is considered by further increases in SOD and GSH-Px activity in the brain. Similar results for MDA were observed in both the liver and brain as well. Our findings suggest that ED consumption alone or combination with ethanol may represent a significant public health concern.

Ethnopharmacological relevance Styrax liquidus is a resinous exudate (balsam) obtained from the wounded trunk of the Liquidambar orientalis Mill. (Hamamelidaceae). Styrax has been used for treatment of various ailments in Turkish folk medicine such as skin problems, peptic ulcers, nocturnal enuresis, parasitic infections, antiseptic or as expectorant. Aim of study In spite of frequent use of styrax in Turkish folk medicine as well as once as a stabilizer in perfumery industry, negative reports have been noticed by the international authority for restriction its use based on some limited evidences from an in vitro study. The aim of the present study was to evaluate the genotoxic and cytotoxic potential of styrax and its ethanolic extract using in vivo and in vitro assays, as well as an antimutagenic assay and also to determine its phenolic constituents with chromatographic analysis. Materials and methods In vitro mutagenicity and antimutagenicity of styrax and its ethanolic extract were evaluated by Ames test performed on Salmonella TA98 and TA100 strains with and without metabolic activation (10– 30,000 µg/plate). The genotoxicity was also studied in vivo by chromosomal aberrations assay on bone marrow of Balb C mice with different its concentrations (500–2000 mg/kg body weight). Cytotoxicity has been evaluated by the MTT assay using L929 cell line. Its phenolic constituents were determined by HPLC analysis. Results Genotoxicological investigations of styrax or its ethanolic extract showed that none of the tested concentrations induced a significant increase in the revertant number of TA98 and TA100 strains with or without metabolic activation, indicating no mutagenicity to the tested strains. Also results indicated that up to 2000 mg/kg body weight, styrax is not genotoxic in mammalian bone marrow chromosome aberration test in vivo. In cytotoxicity study, the IC50 values of styrax and its ethanolic extract were found to be 50.22±1.80 and 59.69±11.77 µg/mL, respectively. Among the studied reference standards the major phenolic acids in styrax balsam was found to be p-coumaric acid (2.95 mg/g), while in its ethanolic extract not only p-coumaric acid (11.46 mg/g), but also gallic acid (1.60 mg/g) were found to the main components. Conclusion The findings of the present study provide scientific basis to the safety of styrax from the viewpoint of genotoxicity risk, and in fact, it was found to be beneficial against genotoxicity.

ALC67 is an N-acylated thiazolidine compound with promising anticancer activity that led to the recent discovery of a series of 3-propionyl thiazolidine-4-carboxylic acid ethyl esters as a family of novel antiproliferative agents. Since the mutagenic and genotoxic properties of marketed anticancer molecules constitute a main issue to be addressed, this study focused on the analysis of the mutagenicity, antimutagenecity, and genotoxicity of this molecule. The mutagenicity and antimutagenicity of ALC67 were evaluated by Ames test performed on Salmonella TA98 and TA100 strains. The genotoxicity of this molecule was investigated in the chromosomal aberration assay on human lymphocytes. All results revealed that the analyzed structure is not mutagenic in the two Salmonella strains tested and was not genotoxic in human lymphocytes in vitro. On the other hand, it showed a weak antimutagenic effect in these two bacterial strains. The above results indicate that after performing some more mutagenicity assays using the other recommended strains, this compound can be safely used for the development of new structures exhibiting anticancer activities.

Predictive toxicology plays an integral role in determining the toxicological profiles of chemicals for safety assessment. Vitamin D is an essential vitamin for the regulation of calcium absorption and homeostasis, as well as the treatment and prevention of several diseases such as rickets and osteomalacia. According to European Medicines Agency (EMA) Guideline on setting health-based exposure limits for use in risk identification in the manufacturing of different medicinal products in shared facilities, permitted daily exposure (PDE) calculation for active pharmaceutical ingredients (APIs) should be done by the medicinal product producers. PDE calculation is mainly based on critical toxicological endpoints such as repeated dose toxicity, genotoxicity, carcinogenicity, developmental and reproductive toxicity, and hypersensitivity potential. During this procedure, critical toxicological endpoints data of an API can be used to predict the PDE of another API that has a similar chemical structure. In the present paper, human toxicological endpoints of vitamin D2, D3, and their metabolites were evaluated and afterwards the data gaps in the toxicological endpoints were filled by forming a category. The read-across was justified by the structural and metabolic similarities. Molecular similarity and mechanistic relevance were found to be substantial, resulting in low uncertainty. The untested vitamin D analogs within the category can be read across with confidence to complete the data gaps related to the human health endpoints. © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group.

The level of arsenic, lead, cadmium, and aluminum in molasses produced by traditional and industrial techniques were investigated. The metal-induced non-carcinogenic and carcinogenic risks were calculated. All samples had a target hazard quotient and index ?1 indicating no undue non-carcinogenic risk from exposure to a single or multiple toxic elements. Three samples produced traditionally exceed threshold limit of acceptable cancer risk. This assessment and the observation of higher levels of toxic metals in traditionally produced molasses is a concerning point for public health and the national authority needs to increase its supervision on the traditional food production. © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group.

The circadian rhythm is constituted by genes/proteins, such as Cryptochrome (Cry). Medications including general anesthetics can alter these genes/proteins thus toxicity occurs. We claim that activation of Cry may contribute to the reduction of anesthetic-induced oxidative stress. In this study, the effect of combination therapy of Cry activator, KL001 with isoflurane was investigated. Twenty-four mice were divided into 4 groups as control, KL001, isoflurane, and KL001 plus isoflurane. The Cry levels and oxidative stress parameters including malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) were investigated. The results showed decreased MDA level in erythrocyte and liver and CAT activity in liver whereas increased GSH-Px activity in liver and brain and SOD activity in erythrocyte, kidney, and brain, in the isoflurane group. Isoflurane remarkably changed the oxidative stress parameters in the brain. Moreover, we found decreased Cry level in plasma, liver, and brain in the isoflurane group. KL001 decreased isoflurane-induced oxidative stress and increased Cry level inhibited by isoflurane. In conclusion, our data indicated that the potential oxidative stress of isoflurane can be reduced by triggering the Cry level with a synthetic activator. Further research is needed to establish the relationship between KL001 and drug-induced oxidative stress. © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group.

Thirty-two novel urea/thiourea compounds as potential kinase inhibitor were designed, synthesized and evaluated for their cytotoxic activity on breast (MCF7), colon (HCT116) and liver (Huh7) cancer cell lines. Compounds 10, 19 and 30 possessing anticancer activity with IC 50 values of 0.9, 0.8 and 1.6 µM respectively on Huh7 cells were selected for further studies. These hit compounds were tested against liver carcinoma panel. Real time cell electronic sensing assay was used to evaluate the effects of the compounds 10, 19 and 30 on the growth pattern of liver cancer cells. Apoptotic cell death and cell cycle analysis upon treatment of liver carcinoma cells with hit compounds were determined. A significant apoptotic cell death was detected upon treatment of Huh7 and Mahlavu cells with compound 30 after 48 h of treatment. Additionally, compound 10 caused cell cycle arrest at G0/G1 phase. Mutagenicity of hit compounds was evaluated. Assertively, these compounds were not found to be mutagenic on Salmonella typhimurium strains TA98 and TA100. To understand the binding modes of the synthesized compounds, molecular docking studies were performed using the crystal data of VEGFR and Src-kinase enzymes in correlation with anticancer activities. © 2018 Marmara Üniversitesi: SAĞ-C-DRP-111115-0502 Türkiye Bilimsel ve Teknolojik AraÅ?tirma Kurumu This work was supported by the Research Fund of Marmara University , project number: SAĞ-C-DRP-111115-0502. The authors are grateful to DEVA Pharmaceuticals for donation of Imatinib mesylate and 4-methyl- N 3 -[4-(pyridin-3-yl)pyrimidin-2-yl]benzene-1,3-diamine specimens for our research. During this research, Aslı Türe was Granted by the Scientific and Technological Research Council of Turkey (TÜBİTAK) under the National Scholarship Programme for PhD Students in Natural Sciences, Medical Sciences, Social Sciences and Humanities and Engineering and Technological Sciences.

Objectives A new HPLC method was developed and validated for the determination of some phenolic compounds; gallic acid, chlorogenic acid, epigallocatechin, caffeic acid, vanillin, p-coumaric acid, rutin, and quercetin in some local wine and fruit wine samples. Materials and methods Analyses were performed on a Zorbax Eclipse C18 column (4.6 x 150 mm, 3.5-µm particle size) using a gradient system. Mobile phase A was a 10-mM phosphoric acid solution and mobile phase B was methanol using a flow rate of 1 mL/min. Phenolic components were monitored using a DAD at three different wavelengths. Results The developed and validated method was generally linear between the 1-100 ppm concentration range. Recovery values were obtained in the range of 95-105% and repetitive. The method was successfully applied to investigate the phenolic profiles of different wine samples. Conclusion As a result of the study, an accurate, sensitive and reliable HPLC-DAD method was developed. The method was successfully used to determine the concentrations of antioxidant phenolic constituents from some local wine extracts.

Natural products can present remarkable biological and pharmacological activities. In traditional medicine, plants have been used historically in treating cancer, infections, and other inflammatory conditions.Verbascoside and catechin are widespread polyphenolic plant compounds that could play a role in the anti-inflammatory and health-promoting effects of plants and plant extracts.This study compares the potential cytotoxic effects of polyphenols verbascoside and catechin (6.25-200 µM) on human peripheral blood mononuclear cells (PBMC) for 48 h and myelomonocytic THP-1 and THP-1 Blue cells for 24 h. The effects of the compounds on immune activation markers such as indoleamine 2,3-dioxygenase (IDO) activity as well as on neopterin formation and nuclear factor-κB (NF-κB) activation were investigated. Cytotoxicity of the compounds was tested using Cell-Titer Blue assay.Verbascoside exhibited significant suppressive effects in mitogen-stimulated PBMC on tryptophan breakdown (50 µM; IC50 value: 58.6 µM) and the production of neopterin (6.25 µM; IC50 value: 217 µM). These effects correlated with a decline in cell viability, while THP-1 Blue cells were less sensitive. NF-κB activity was slightly enhanced at lower concentrations (50 µM verbascoside) in stimulated cells and at the highest concentration used in unstimulated cells. Catechin had no relevant effects on cell viability and on the tested inflammation markers, except NF-κB activation in THP-1 Blue cells.The results obtained show that verbascoside and catechin represent effective compounds which interfere with immunobiochemical pathways that are highly relevant for immunosurveillance and competing virus infections.

This study was designed to evaluate the effects of acetaminophen (APAP) and N-acetylcysteine (NAC) in combination on the protective effect of NAC for possible APAP toxicity determining oxidative stress and inflammation parameters in a rat model. DMSO as vehicle, 50 mg/kg APAP and 50 mg/kg APAP plus 100 mg/kg NAC were administrated to Wistar Albino rats by intra-peritoneal for five days. Plasma TNF-α, IL-2 and IL-6 levels and level of malondialdehyde (MDA), glutathione peroxidase (GSH-Px), catalase (CAT) and superoxide dismutase (SOD) activities in liver and kidney were analyzed. APAP administration produced an increase in hepatic and renal MDA levels and co-administration of APAP plus NAC resulted in decreases in the kidney MDA levels and an increase in hepatic and renal superoxide scavenging enzyme, SOD, activity. Taken together, the results of this study suggest that combination of APAP and NAC may be a valuable combination to protect hepatotoxicity and nephrotoxicity induced by APAP. Furthermore, pharmaceutical preparation with combination of APAP and NAC may be useful alternative to prevent from possible APAP related toxicity. However, further investigations are needed to understand the underlying protection mechanism of NAC combination with APAP

A novel high performance liquid chromatography method has been developed and validated for the simultaneous determination of furfural and hydroxymethylfurfural in 18 honey samples. An Agilent Poroshell 120 EC-C18 150x3 mm 2.7 mu m particle sized column and isocratic elution with a 0.5 mL/min flow rate were used. The mobile phase was 10mM pH 2.5 phosphate buffer and acetonitrile and monitoring of analytes was carried on using a DAD detector at 284 nm wavelength. The method was validated according to USP guideline in terms of accuracy, precision, specificity, linearity and range\ robustness and ruggedness. According to the obtained results, the concentration levels of hydroxymethylfurfural were between 19.56-209.42 mg/kg in honey samples. Observed concentration values of HMF for 5 honey samples were higher than requirements and the highest level of hydroxymethylfurfural was observed in a thyme honey sample (209.42 mg/kg). The concentration values of furfural found in honey samples were in the range of 0.34-2.23 mg/kg. The highest level of furfura was determined in the thyme honey sample (2.23 mg/kg) also containing the highest concentration of hydroxymethylfurfural. In this study, the margins of exposure to furfural were also calculated for investigated honey samples. The margins of exposure for all analyzed samples were above the value of 100, indicating the safety of samples regarding to furfural exposure. The excessive hydroxymethylfurfural contents in some samples is a concerning point for public health and the national authority needs to increase its supervision on the honey.

Hydrogen cyanide (HCN) poisoning due to amygdalin (AMY) in apricot seeds is one of the public health issues in Turkey. The aim of this study was to investigate the AMY content of 13 different apricot seeds including bitter and sweet ones, and which are either sulfurized or roasted. The AMY content was determined by a high-performance liquid chromatography. Release of HCN was predicted and total amount of seeds which can cause poisoning was calculated. The mean AMY content of bitter seeds was 26 ± 14 mg g−1 and that of sweet seeds was 0.16 ± 0.09 mg g−1. The consumption of small amounts of bitter seeds may cause cyanide poisoning.

The genotoxicity potential of silver nanowires synthesized via the solution-based polyol method has been investigated. They were found to be non-mutagenic in three Salmonella strains and were not genotoxic in a clastogenicity assay in mice. Residual surfactant was found to have an effect on the toxicological properties of the nanowires by increasing the rate of Ag+ release. Residual surfactant can be easily degraded via a UV treatment. © 2017 Informa UK Limited, trading as Taylor & Francis Group.

Background Evaluations of silver in both nanoparticle (Ag-NPs) and ionic forms indicate some adverse effects on living organisms, but little is known about their potential for developmental toxicity. In this study, developmental toxicity of Ag-NPs (from 0.2 to 20 mg/kg/day) and ionic Ag (AgNO3, 20 mg Ag/kg/day) were investigated in rats. Methods Animals were dosed by gavage from gestation day 7 − 20. The day after parturition, dams and pups were sacrificed and Ag level assessed in several maternal and pup organs. In addition, hepatotoxicity and oxidative stress parameters and histopathology were evaluated. Results No treatment related effects were found for gestational parameters including pregnancy length, maternal weight gain, implantations, birth weight and litter size at any dose level of Ag-NPs. Maternal weight gain was lower in dams receiving AgNO3 compared to the other groups, suggesting that the ionic form may exert a higher degree of toxicity compared to the NP form. Tissue contents of Ag were higher in all treated groups compared to control dams and pups, indicating transfer of Ag across the placenta. The findings furthermore suggest that Ag may induce oxidative stress in dams and their offspring, although significant induction was only observed after dosing with AgNO3. Histopathological examination of brain tissue revealed a high incidence of hippocampal sclerosis in dams treated with nanoparticle as well as ionic Ag. Conclusion The difference in offspring deposition patterns between ionic and NP Ag and the observations in dam brain tissue, requires scrutiny, and, if corroborated, indicate that ionic and NP forms maybe need separate risk assessments and that the hazard ratings of silver in both ionic and nanoparticle forms should be increased, respectively. Trial registration Not applicable. Graphical abstract Developmental Toxicity of Ag-NPs.

Energy drinks (ED) are containing large doses of metabolic stimulants and its use with ethanol has increased dramatically among young adults. In this study, we examined the effects of ED exposure either alone or in combination with ethanol on oxidative stress parameters including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and lipid peroxidation parameter malondialdehyde (MDA) in rat. Some histopathological findings were also evaluated. ED exposure led to a dose-dependent increase in liver MDA compared to the control indicating oxidative damage. Histopathological findings also revealed that ED alone may generate liver damage. Ethanol exposure increased MDA level and SOD, CAT, and GSH-Px activity in both the brain and the liver. The combination of ethanol and ED produced greater damage which is considered by further increases in SOD and GSH-Px activity in the brain. Similar results for MDA were observed in both the liver and brain as well. Our findings suggest that ED consumption alone or combination with ethanol may represent a significant public health concern.

Hot-dip galvanization is a zinc-coating process to protect the metal items from corrosion. Zinc oxide nanoaerosol fume rising from hot metal bath surface in nano dimensions contains the greatest risk for workers in galvanization process. In the present study, it was evaluated whether inhalation of zinc causes any alteration in cellular immunity and tryptophan degradation by measuring neopterin, tryptophan, kynurenine, and zinc levels in 63 male galvanization workers and 23 male office personnel as controls. Serum and urinary zinc levels were found as 14.90 ± 0.90 and 102 ± 4.7 µg/dL in workers while 12.87 ± 1.45 and 75 ± 4.2 µg/dL in controls, respectively (both, p< 0.05). Similarly, the mean urinary neopterin levels and serum neopterin and kynurenine levels were found to be statistically higher in galvanization workers than the controls (all, p< 0.05). Significant correlations were found between urinary neopterin levels and kynurenine to tryptophan ratio or serum zinc levels. The results indicated cellular immune activation by occupational zinc exposure. It was estimated that neopterin, in parallel with kynurenine pathway, could reflect occupational exposure to zinc nanoaerosols and might be useful in early diagnosis of immune alterations due to nano-scale exposures. © Springer Science+Business Media New York 2012.

Toxic metals are one of the significant groups of chemical contaminants that humans are exposed to by oral, inhalation, and dermal routes. Exposure to these chemicals begins with intrauterine life and continues during lactation period at the first years of life. Breastfeeding has a much more special place than other nutrition options for infants. However, when possibility of contaminant transfer by breast milk is considered, its safety and quality is essential. Regarding infant and mother health and limited number of information on this field in Turkey, measuring contamination levels in breast milk is important. Therefore, in the present study, lead (Pb), cadmium (Cd), nickel (Ni), and arsenic (As) levels were measured by atomic absorption spectrometry in 64 breast milk samples obtained from mothers from Ankara, Turkey. Pb and Ni levels in breast milk samples were found to be 391.45 +/- 269.01 mu g/l and 43.94 +/- 33.82 mu g/l (mean +/- SD), respectively. Cd was found only in one of 64 samples, and the level was 4.62 mu g/l. As level was below the limit of quantification (LOQ, 7.6 mu g/l) in all samples. These findings will accurately direct strategies and solutions of protection against contaminants in order to reduce their levels in biological fluids.

Cosmetics are one of the most common reasons for hospital referrals with allergic contact dermatitis. Because of the increased use of cosmetics within the population and an increase in allergy cases, monitoring of heavy metals, especially allergen metals, is crucial. The aim of this study was to investigate the concentration of allergen metals, nickel (Ni), cobalt (Co), and chromium (Cr), in the most commonly used cosmetic products including mascara, eyeliner, eye shadow, lipstick, and nail polish. In addition, for safety assessment of cosmetic products, margin of safety of the metals was evaluated. Forty-eight makeup products were purchased randomly from local markets and large cosmetic stores in Istanbul, Turkey, and an atomic absorption spectrometer was used for metal content determination. Risk assessment of the investigated cosmetic products was performed by calculating the systemic exposure dosage (SED) using Scientific Committee on Consumer Safety guideline. According to the results of this investigation in all the samples tested, at least two of the allergen metals, Ni and/or Co and/or Cr were detected. Moreover, 97% of the Ni-detected products, 96% of Cr- and 54% of Co-detected products, contained over 1 μg/g of this metals, which is the suggested ultimate target value for sensitive population and thereby can be considered as the possible allergen. On the basis of the results of this study, SED of the metals was negligible; however, contact dermatitis caused by cosmetics is most probably due to the allergen metal content of the products. In conclusion, to assess the safety of the finished products, postmarketing vigilance and routine monitoring of allergen metals are very important to protect public health.

Suyun kalitesi halk sağlığı için çok önemlidir. Ancak sularda nitrit ve nitrat düzeyleri hala önemli bir kontaminasyon problemidir. Bu çalışmanın amacı İstanbul'un farklı bölgelerinden toplanan musluk suyu ve çeşme sularında toplam nitrit ve nitrat düzeylerini tespit etmektir. Bu amaçla çeşitli bölgelerden musluk suyu örnekleri Kasım 2013'den Mart 2014'e kadar toplanmış ve değerlendirilmiştir. Su örneklerinde ortalama toplam nitrit ve nitrat düzeyleri Kasım, Aralık 2013 ve Şubat 2014 ile karşılaştırıldığında Mart 2014'te en yüksektir. ABD Çevre Koruma Ajansına göre, musluk sularından iki tanesi ve kuyu sularından üç tanesi toplam nitrat ve nitrit için maksimum kabul edilebilir konsantrasyonu (10 ppm) aşmaktadır. Ancak tüm örneklerde bu düzeyler Türkiye'nin resmi dökümanlarında bildirilen maksimum kabul edilebilir düzeylerin altındadır. Ayrıca, yıllar arası değişimi saptamak için, bir önceki yıla ait su örnekleri de değerlendirilmiştir. Sonuçlar Aralık 2013-Şubat 2014 döneminde toplam nitrit ve nitrat düzeylerinin Aralık 2012-Şubat 2013 dönemine göre %2, 10 ve 18 oranında azalma göstermiştir. Sonuçlarımıza göre, mevsimsel değişim göz önüne alınarak, halk sağlığının korunması için sularda nitrit/nitrat düzeyleri rutin olarak kontrol edilmelidir. Water quality has a major importance for public health. However, nitrite and nitrate levels in water are still an important contamination issue in the world. The aim of this study was to determine the levels of total nitrite and nitrate in public water (tap water) and wells from different districts of Istanbul city and to evaluate the seasonal variation from November 2013 to March 2014. The average levels in tap waters were highest in March 2014 compared with November, December 2013 and February 2014. Two of the tap water and 3 of the well water samples exceed the maximum acceptable concentration according to the U.S. Environmental Protection Agency (10 ppm). However, these levels were still lower than the maximum allowable limits reported in official documents of Turkey. Also, in order to determine the annual variation, tap water samples were collected between December 2012 and February 2013 and evaluated for total nitrite and nitrate levels. Results showed that total nitrite and nitrate levels during December 2013 and February 2014 were decreased in the ratio of 2, 10 and 18% compared to the same months during December 2012 and February 2013. In conclusion, our results suggested that due to seasonal and annual variations, nitrite and nitrate levels of waters should be routinely controlled to prevent various health hazards.

This study was designed to evaluate the effects of in vitro gastrointestinal simulation method on the antioxidant potentials and phenolic profile of some Turkish fruit wines and to compare the results with a Turkish red wine prepared from native grape varieties (Papazkarasi). For this purpose, blueberry, black mulberry and cherry wines were studied since they are widely consumed in Turkey. Papazkarasi wine was chosen due to the lack of studies regarding this type of wine. Antioxidant potentials of samples were measured with four different methods: DPPH radical-scavenging activity, H2O2-scavenging activity, cupric reducing capacity and total antioxidant capacity assays. The phenolic profiles of samples were evaluated by the determination of total phenolic content and HPLC-DAD analysis of seven different molecules. The results of this study provided information not only the effect of gastrointestinal digestion on parameters mentioned above, but also the bioaccessibility about the phenolic compounds found in these four different wine samples. © 2015 Elsevier Ltd.

Background Dried fruits of Berberis crataegina (Berberidaceae) have been frequently consumed as food garniture in Turkish cuisine, while its fruit paste has been used to increase stamina and in particular to prevent from cardiovascular dysfunctions in Northeastern Black Sea region of Turkey. This study investigated this folkloric information in order to explain the claimed healing effects as well as to evaluate possible risks. Methods Total phenolic, flavonoid and proanthocyanidin contents and antioxidant capacity of the methanolic fruit extract were evaluated through several in vitro assays. The cytotoxic and genotoxic effects of B. crataegina fruit extract were also assessed in both cervical cancer cell line (HeLa) and human peripheral blood lymphocytes. Results The extract showed protective effects against ferric-induced oxidative stress and had a relatively good antioxidant activity. It also ameliorated the H2O2 mediated DNA damage in lymphocytes, suggesting the protective effect against oxidative DNA damage. Conclusion The methanolic extract of B. crataegina fruits may be a potential antioxidant nutrient and also may exert a protective role against lipid peroxidation as well as oxidative DNA damage.

Atropine Intoxication in a Child after Accidental Ingestion of 200 mg Atropine Sulfate - A Case Report Atropine systemic toxicity may causes the anticholinergic toxidrome including pupillary, mucous membranes, skin, urinary, gastrointestinal, cardiac, and central nervous system symptoms. A 6-year-old boy admitted to the emergency department with agitation, vomiting, and fever with a suspect ingestion of atropine sulfate solution. The patient was hospitalized, intubated, sedated with midazolam and mechanically ventilated. Gastric lavage was performed. After treatment with active charcoal, neostigmine and afterwards physostigmine were administered. Atropine sulfate was detected in the blood sample by using high-performance liquid chromatography-diod array detector method. Patient had supportive care until his symptoms resolved. At the end of the fourth day, patient was discharged in a healthy state except bilateral mydriasis which may continue for a week..

… European Soc Toxicol

Onceki calismalardan elde edilen 1h ve 1j adli bilesikler potansiyel antikanser aktiviteye sahiptir. Antikanser ilaclarin mutajenik ve genotoksik ozelliklerinin bu ilaclarin arastirilmasinda temel konuyu olusturmasi sebebiyle, calismada soz konusu molekullerin mutajenite ve genotoksisite analizleri uzerinde durulmustur. 1h ve 1j Molekullerinin mutajeniteleri Salmonella TA98 ve TA100 suslari ile Ames testi uygulanarak belirlenmistir. 1j Bilesigi TA98 bakteri susu uzerinde mutajen bulunmustur. Ancak, 1h bilesiginin TA 100 ve TA98 suslari ile S9 varliginda ve yoklugunda mutajenik aktiviteye sahip olmadigi gosterilmistir. 1h Bilesiginin genotoksisitesi insan lenfositleri uzerinde yapilan kromozomal aberasyon testi ile degerlendirilmis olup genotoksik bir risk olusturmadigi saptanmistir. Butun sonuclar degerlendirildiginde, 1h’nin iki farkli Salmonella susu uzerinde yapilan calismada mutajenik aktivitesi olmadigi ve kromozom aberasyon testinde genotoksik olmadigi saptanmistir. Bu nedenle, sonuclari belirtilen molekulun mutajenik ve genotoksik etkileri olmadigi icin yeni bir antikanser ilac olarak umut verici oldugu gorulmustur. Guvenle kullanilabilecek antikanser aktivite sergileyen yeni bir molekulun varligini gostermek icin yukaridaki analizlere ek olarak Ames testi tavsiye edilen diger bakteri suslariyla ve in vivo deneylerle desteklenmelidir.

This study evaluated the content of cadmium (Cd), lead (Pb), and nickel (Ni) in 105 hair care products commercially available in Turkey. Cd, Pb, and Ni were detected in 40%, 21.91%, and 94.29% of the samples, respectively. Maximum Cd concentrations were detected in two shampoo samples, and the highest Pb level was found in a hair conditioner, all of them were herbal-based formulations. The highest mean levels of Ni were detected in hairstyling agents. The overall results were lower than the Canadian and German regulatory limits; however, according to the European Council Directive and Turkish Cosmetic Legislation, Cd, Pb, and Ni are listed as the substances that are prohibited in any amounts in cosmetics. Moreover, Ni content of 17.14% of the samples was above the limit of allergic contact dermatitis. It is known that these toxic metals tend to accumulate in body and prolonged use of them may potentially pose threat to human health. Thus, regular market monitoring and safer limits should be seriously considered especially for susceptible groups of the population like the pediatric group.

Son yillarda yurutulen bilimsel arastirmalar bitki caylarinin ve balin tasidiklari antioksidan etkili bilesenlerin bircok akut ve kronik hastaliklarin gelisme riskini azaltmaya yardimci olabilecegini gostermektedir. Ancak bitki caylarinin icerisine tatlandirici olarak bal ilave edilmesi ile antioksidan kapasitede ne gibi bir degisim olabilecegi konusu aydinliga kavusmamistir. Bu calismanin amaci, Turkiye’de satilan 9 farkli karisik veya saf bitki cay orneginin total antioksidan kapasitesinin hem tek baslarina hem de cam bali veya cicek bali ilavesinden sonra TOAK degerlerindeki olasi degisimin tespit edilmesidir. Bir fincana esdeger 100 ml caydaki en yuksek TOAK degeri melisa, siyah cay ve beyaz cayda gorulmustur. Bunlari sirasiyla yesil cay > adacayi > ekinezya > papatya > zencefil > ihlamur takip etmistir. Bitki caylarinin antioksidan etkisinin hem cam hem de cicek bali ilavesi ile paralel olarak arttigi, 7 g bal ilavesinin 3 g bala gore daha yuksek etkinlik gosterdigi gozlemlenmistir. Bazi bitki caylarinda (melisa, adacayi, ihlamur, papatya, limonlu zencefil) cam bali ilavesinin cicek balina oranla antioksidan etkinin daha fazla yukseldigi gorulurken, bazilarinda (ekinezya) cicek bali ilavesinin daha etkili oldugu tespit edilmistir. Sonuc olarak, calismamizda bitki caylarina bal ilavesinin antioksidan aktiviteyi onemli olcude artirdigi ve gunde en az 1 defa balli cay icmenin vucudu serbest radikallere karsi koruyucu etki gosterebilecegi ve ozellikle oksidatif strese bagli gelisen hastaliklarda destekleyici tedavi olarak kullanilabilecegi dusunulmektedir. Ancak bu kombinasyonunun koruyucu mekanizmasinin anlasilmasi icin ileri/ek calismalar gerekmektedir

Metals including lead (Pb), cadmium (Cd), arsenic (As), and nickel (Ni) have been used for different purposes in industry. These metals can be found in the colourful components of toys such as clothes. Due to the fact that these metals cause different health problems, the usage of them in industry is still continuing to be regulated strictly. The aim of this study was to investigate the leaching of the above mentioned metals from dresses of toy samples marketed in Turkey. A total number of nine toys manufactured by six different countries were purchased and analysed by atomic absorption spectrophotometer for Pb, Cd, Ni and As leached from dresses of samples.The results were as follows: Pb levels were ranged from 0.03 to 1.78, Cd was from 0.37 to 21.11, Ni was from 0.37 to 21.11 mg/kg and As was under the detection limit. According to the measurements, Pb levels of all toy samples were below the levels stated in Turkish Standards Institute (TSE) but one sample’s result was high. Cd and As levels were observed to be far below the threshold limis stated at TSE standard. There is no limit value for Ni in that standard. In spite of international regulations, some of toy samples can include significant amount of metals. These experimental evidences suggest that surveillance on toys for their metal levels should be done regularly for children’s safety. © 2014, Turkish Pharmacists Association. All rights reserved.

The potential effects of globularifolin, an acylated iridoid glucoside, on cell survival, inflammation markers and free radicals scavenging were investigated. Viability assay on human myelomomonocytic cell line THP-1 and human peripheral blood mononuclear cells (PBMC) using the Cell-Titer Blue assay proved that globularifolin had no toxic effect at the tested concentrations. Conversely, it is proportional to the dose globularifolin increased growth of THP-1 cells (p