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Seaweeds are well known for having a wealth of nutritional benefits and providing ecological support to associated fauna. Seasonality influences the biochemical characteristics, affecting their ecological and economic values. In the present study, we evaluated pigments, primary and secondary metabolites, minerals, and antioxidant properties of green seaweed Chaetomorpha antennina growing on the intertidal rocks along the Covelong coast, India, in different seasons (from June 2019 to March 2020). Significant variations were found in the levels of antioxidants, minerals, and metabolites in different seasons, e.g., amino acid levels were the highest in post-monsoon and the lowest in summer. In monsoon, we found the highest concentration of fatty acids in the thalli. Lipid peroxidation and total antioxidant activity were at their maximum levels during post-monsoon, which indicated oxidative damage responses. No significant variations were found in the levels of photosynthetic pigments. The outcomes indeed suggested seasonal variations in the biochemical and nutrient profile of C. antennina. We suggest that the harvesting/collection of C. antennina for different nutrients and metabolites should be performed in the respective seasons. [ABSTRACT FROM AUTHOR]

In this study, calcium phosphate nanoparticles-based (STCNV) and montanide oil adjuvant vaccine (STOAV) containing outer membrane proteins (Omps) of S. Typhi were evaluated for inducing oxidative stress indicators [reduced glutathione (GSH), lipid peroxidation (LPO), catalase, superoxide dismutase (SOD), and total protein] in the tissues of mice after vaccination. The GSH levels though slightly high in the liver, kidney, and lungs of STCNV group were not significantly different from STOAV and the control group (STC). There was no significant difference in LPO levels in any group for any tissue. The significantly lower activities of catalase were observed in the kidney and lungs of the STCNV group as compared to STOAV and STC group, while in the liver, STCNV group revealed lower catalase activity in comparison to the control group. No significant difference in the SOD activities between the two vaccinated groups was observed. The total protein contents in all the organs showed no significant difference in the vaccinated and the control group. The vaccines may induce long-term inflammatory response and consequently damage vital organs; this study revealed no long-term oxidative stress in all the three vital organs, suggesting that these vaccines may not cause oxidative damages in the vital organs of mice. [ABSTRACT FROM AUTHOR]

Oxidative stress, due to reactive oxygen species (ROS) or free radicals, can increase cardiovascular risk factors (CRFs). Lifestyle, environment, and genetics are the primary reasons for ROS generation. The role of genetics in the causation of CRFs mediated by ROS is still elusive. The present study aimed to determine the prevalence of null genotypes of oxidative stress genes (GSTM1 and GSTT1) and cardiovascular risk factors (CRFs) in an urban population. The association of GSTM1 & GSTT1 null genotypes with CRFs was also assessed in this study. A total of 40 participants (permanent residents of Chandigarh, India) were recruited. Anthropometric and physiological data were collected along with blood samples. Biochemical and molecular analysis were performed on all the collected blood samples. More than 90% of the participants had high blood pressure (HBP), 70% had obesity (OBS), and 40% had postprandial hyperglycemia (PPH). The null-genotype of GSTM1 and GSTT1 exhibited 47.50% and 7.50% of participants, respectively. GSTM1 and GSTT1 null genotypes were higher in males than females (50% vs 42.9% and 7.7% vs 7.1%). Agewise distribution showed that the absence of GSTM1 genotype was more in older participants (56.5% vs 35.3%) while GSTT1 genotype was more absent in younger participants (11.8 % vs 4.3%). Participants with null genotypes had trends of high CRFs, but only diastolic blood pressure (DBP) was significantly high. Although, mean arterial pressure (MAP) was also on the verge of significance. Odd ratio analysis showed a 2.383-fold risk of hyperglycemia in participants with either null genotypes. The present study concluded that studied participants are at greater risk of cardiovascular diseases due to high trends of CRFs. High CRFs may be related to the null genotype of GSTM1 and GSTT1 in the urban environment. Further studies with a bigger sample size are warranted to establish the results of the present study. [ABSTRACT FROM AUTHOR]

The intracellular nature of Brucella leads to rise in oxidative stress due to bacterial invasion, particularly at the site of predilection spleen and lymph nodes. The present study aimed to evaluate the erythrocytic and tissue specific oxidative stress responses induced during oil adjuvant killed Brucella melitensis vaccination. The results of the study clearly implicated a significant increase in level of catalase, and superoxide dismutase (SOD) activity and lipid peroxidation (LPO), and total protein content in erythrocytes after vaccination. The activity of glutathione-S-transferase (GST) was unaltered during the period of experiment. The catalase activity and GSH content was significantly increased in lung and spleen tissues. The tissues GST levels increased significantly in all tissues, while tissue SOD level increased significantly only in lung tissues. Thus, it can be inferred that oil adjuvant based Brucella vaccine induces negligible signs of inflammatory pathophysiology and supports the development of significant level of protection against virulent Brucella challenge. [ABSTRACT FROM AUTHOR]

Brucella melitensis, mainly responsible for human brucellosis, is considered as biological warfare. Being intracellular in nature Brucella induces oxidative stress due to bacterial invasion in organs like spleen and lymph nodes. The present study was aimed to evaluate the specific oxidative stress responses in erythrocytes and tissues induced by intranasal inoculation of killed Brucella whole cell protein antigen coupled with sodium acrylate nanoparticle adjuvant. Glutathione mediated nonenzymic antioxidant defense system and catalase have been observed to play a critical role in intracellular antioxidant defenses in vaccinated animals and also in maintaining an excellent milieu to induce an active immune potential. The antioxidant defenses in erythrocytes, liver, kidneys, lungs and spleen of vaccinated mice also maintained excellent redox homeostasis required for quality and effective protection without inflammatory pathophysiology. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the effect of 460 nm light-emitting diode (LED) on the inactivation of foodborne bacteria. Additionally, the change in the endogenous metabolic profile of LED illuminated cells was analyzed to understand the bacterial response to the LED illumination. Six different species of bacteria ( Bacillus cereus , Listeria monocytogenes, Staphylococcus aureus , Escherichia coli O157:H7, Pseudomonas aeruginosa and Salmonella Typhimurium) were illuminated with 460 nm LED to a maximum dose of 4080 J/cm 2 at 4, 10 and 25 °C. Inactivation curves were modeled using Hom model. Metabolic profiling of the non-illuminated and illuminated cells was performed using a Liquid chromatography–mass spectrometry system. Results indicate that the 460 nm LED significantly (p < 0.05) reduced the populations of all six bacterial species. For example, the population of S. aureus reached below detection limit within 7 h. B. cereus was most resistant to photo-inactivation and exhibited about 3-log reduction in 9 h. Metabolic profiling of the illuminated cells indicated that several metabolites e.g. 11-deoxycortisol, actinonin, coformycin, tyramine, chitobiose etc. were regulated during LED illumination. These results elucidate the effectiveness of 460 nm LED against foodborne bacteria and hence, its suitability as a novel antimicrobial control method to ensure food safety. [ABSTRACT FROM AUTHOR]

The study investigates the potential of Rolipram a phosphodiesterase-4 inhibitor in cognitive deficits induced by streptozotocin (STZ, 3 mg/kg intracerebroventricularly) and natural ageing in mice. Morris water maze (MWM) test was employed to evaluate learning and memory of the animals. Extent of oxidative stress was measured by estimating the levels of brain glutathione (GSH) and thiobarbituric acid reactive species (TBARS). Brain acetylcholinestrase (AChE) activity was also estimated. The brain activity of myeloperoxidase (MPO) was measured as a marker of inflammation. STZ and ageing results in marked decline in MWM performance of the animals, reflecting impairment of learning and memory. STZ treated mice and aged mice exhibited a marked accentuation of AChE activity, TBARS and MPO activity along with fall in GSH level. Further the stained micrographs of STZ treated mice and aged mice indicate pathological changes, severe neutrophilic infiltration and amyloid deposition. Rolipram treatment significantly attenuated STZ induced and age related memory deficits, biochemical and histopathological alterations. The findings demonstrate the potential of Rolipram in memory dysfunctions which may probably be attributed to its anti-cholinesterase, anti-amyloid, anti-oxidative and anti-inflammatory effects. The study concludes that PDE-4 can be explored as a potential therapeutic target in dementia. [ABSTRACT FROM AUTHOR]

Redox homeostasis is crucial for proper cellular functions, including receptor tyrosine kinase signaling, protein folding, and xenobiotic detoxification. Under basal conditions, there is a balance between oxidants and antioxidants. This balance facilitates the ability of oxidants, such as reactive oxygen species, to play critical regulatory functions through a direct modification of a small number of amino acids (e.g. cysteine) on signaling proteins. These signaling functions leverage tight spatial, amplitude, and temporal control of oxidant concentrations. However, when oxidants overwhelm the antioxidant capacity, they lead to a harmful condition of oxidative stress. Oxidative stress has long been held to be one of the key players in disease progression for Huntington’s disease (HD). In this review, we will critically review this evidence, drawing some intermediate conclusions, and ultimately provide a framework for thinking about the role of oxidative stress in the pathophysiology of HD. [ABSTRACT FROM AUTHOR]

The present study has been designed to investigate the potential of Cilostazol a phosphodiesterase-3 (PDE-3) inhibitor in diabetes-induced vascular dementia (Vad) employing Wistar rats. A single dose of Streptozotocin (STZ) was used for the induction of diabetes and subsequent Vad in rats. Memory and learning abilities of rats were evaluated with Morris water maze (MWM) test. Serum glucose, body weight, vascular endothelial function, serum nitrite/nitrate levels, brain oxidative stress levels (viz. brain thiobarbituric acid reactive species and reduced glutathione levels), inflammatory markers ( viz . brain myeloperoxidase activity and neutrophil infiltration in the brain hippocampal area) and brain acetylcholinesterase activity were also tested. Donepezil was used as positive control. Streptozotocin treated animals showed poor performance on MWM indicating impairment of learning and memory abilities with a significant reduction in body weight, vascular endothelial function, serum nitrite/nitrate levels, along with an increase in serum glucose, brain oxidative stress levels, inflammatory changes and brain acetylcholinesterase activity. Treatment with selective PDE-3 inhibitor, Cilostazol significantly attenuated, diabetes-induced impairment of learning and memory; endothelial dysfunction, and changes in various biochemical parameters. It is concluded that selective PDE-3 inhibitor, Cilostazol may be considered as the potential pharmacological agent for the management of diabetes-induced vascular dementia. [ABSTRACT FROM AUTHOR]

Strain of Ganoderma lucidum MDU-7 produce multiple extracellular isoforms of laccase in submerged culture condition using malt extract as a carbon source and copper sulfate as an inducer. SDS–PAGE followed by MALDI–TOF peptide fingerprinting confirmed laccase isozyme with molecular mass of 24–66 kDa. Two laccase isozymes (Glac H1 and Glac L1) were purified from native-PAGE protein purification method and a comparative catalytic and antioxidant study has been performed. Both of the laccase isozymes have optimum temperature and pH at 50 °C and 4.0, respectively. Glac L1 has higher stability in comparison to Glac H1, over wide range of temperature, pH, divalent metal ions and surfactants. The K m values of Glac L1 and Glac H1 determined for guaiacol, ABTS and O -tolidine were 98 μM, 26 μM, 320 μM and 281 μM, 29 μM, 338 μM, respectively. Glac H1, irrespective to its laccase activity and stability, acts as a better antioxidant than Glac L1. [ABSTRACT FROM AUTHOR]

Introduction: Oxidative stress and cytokines play an important role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). We compared the presence of oxidative stress and cytokines in 25 patients with NAFLD with 25 age, sex and BMI-matched patients with chronic viral hepatitis (CVH) and 25 healthy volunteers (HV). Methodology: Oxidative stress was studied biochemically by markers of lipid peroxidation and biochemical assessment of anti-oxidant status and various cytokines were studied by ELISA. Results: Patients with NAFLD had significantly higher levels of malondialdehyde (MDA) (p = 0.000) and conjugated dienes (CD) (p = 0.000) in comparison to HVs. Patients with NAFLD also had significantly higher MDA levels (p = 0.000) in comparison to CVH patients. Patients with NAFLD had significantly lower GSH levels (p = 0.004) in comparison to HVs. Patients with NAFLD had higher GPx activity (p = 0.028) in comparison to HVs. Catalase activity was significantly decreased in both NAFLD (p = 0.001) and CVH patients (p = 0.000) in comparison to HVs. Patients with NAFLD had significantly higher SOD activity (p = 0.000) in comparison to CVH patients. There was no difference in serum levels of IL-1β and TNF-α amongst three groups. Patients with CVH were found to have higher IL-8 serum levels (p = 0.039) in comparison to HVs. CVH patients also had higher TGF-β levels (p = 0.002) in comparison to both NAFLD patients and HVs. Conclusion: Differences in the markers of oxidative stress and anti-oxidant status between NAFLD, CVH and healthy volunteers suggest presence of higher oxidative stress in patients with NAFLD. [Copyright &y& Elsevier]

Purpose: This study examined the effect of liposomal encapsulation of 99mTc-labeled diethylenetriaminepentaacetic acid (metastable technetium labeled DTPA) on its organ distribution and therapeutic effect of optimized neutral liposomal-DTPA against thorium (232Th)-induced liver toxicity and its accumulation in rat animal model. Materials and methods: 99mTc-DTPA was encapsulated in neutral (dipalmitoylphosphatidylcholine:cholesterol) and positively (dipalmitoylphosphatidylcholine:cholesterol:stearylamine) charged liposomes using thin film hydration method. Comparative efficacy of liposomal and free DTPA (11.2 mg/kg) was examined in terms of its effect on 232Th accumulation and subsequent toxicity in the liver and blood of rat administered with 232Th-nitrate (600 μg/kg). Organ distribution of free or liposomal 99mTc-DTPA was determined by solid scintillation counting and 232Th accumulation by Inductively Coupled Plasma-Atomic Emission Spectroscopy. Results: Neutral liposomes encapsulated with 99mTc-DTPA showed more uptake in liver, spleen and blood than with positively charged liposomal- and free- 99mTc-DTPA. Administration of 232Th-nitrate to rat significantly increased the levels of liver toxicity markers and of oxidative injury, which were found to be restored more significantly by neutral liposomal-DTPA than free-DTPA. The accumulation of 232Th in liver and blood of contaminated mice was found to be decreased more significantly by neutral liposomal-DTPA than by free-DTPA. Conclusions: Decorporation and consequent mitigation of 232Th induced toxicity may be significantly improved by liposomal encapsulation of DTPA, a chelating agent. [ABSTRACT FROM AUTHOR]

Abstract: Thiol family of antioxidants has been considered to be the most effective class of radio protective agents. Present study reports a comparative evaluation of antioxidant thiols, namely N-acetyl cysteine (NAC), glutathione (GSH) and thioproline (TP), on gamma radiation-induced damage to human lymphocytes DNA as assessed by micronucleus (MN) formation and comet assay parameters. Pretreatment of cells with NAC, GSH and TP showed significant protection against DNA damage and MN frequency in irradiated lymphocytes (2–4Gy). The magnitude of DNA damage protection was found to be concentration dependent (100–300μM) which followed the order GSH>NAC>TP. Further, antioxidant thiols mediated protection against DNA damage in irradiated lymphocyte showed significant correlation with their ability to decrease intracellular ROS but not to the increase in intracellular GSH. Experiments on the effect of antioxidant thiols on plasmid DNA irradiated under cell free aqueous conditions showed that NAC exerts greater protection than GSH against radiation damage. TP showed similar responses in cellular and plasmid DNA. Greater protection of plasmid DNA by NAC is ascribable to its more potential hydrogen donor ability as revealed by radical chromogen 2,2-diphenyl-1-picrylhydrazyl (DPPH) photometric assay. Thus, present study indicated that radioprotection of lymphocytes DNA by antioxidant thiols are closely correlated to the reduction of cellular oxidative stress, which seems to involve multiple mechanisms. [Copyright &y& Elsevier]

Purpose: Thorium (232Th), a heavy metal radionuclide that targets the liver and skeleton, has been shown to accumulate in the central nervous system at low levels. The present study was aimed to investigate neurobehavioural and neurochemical changes in mice treated with 232Th at sub-lethal doses. Materials and methods: Swiss albino mice were administered intraperitoneally with thorium nitrate. The chelation-based therapeutic effect of calcium diethylenetriamine pentaacetate (Ca-DTPA) was tested on the 232Th-treated mice. 232Th localisation was determined in brain regions by the Inductively Coupled Plasma-Atomic Emission Spectroscopy (ICP-AES) method. Achetylcholine esterase (AChE) activity in different brain regions was evaluated to assess the cholinergic function of mice CNS. Oxidative damage was evaluated by assessing the activities of antioxidant enzymes (i.e., superoxide dismutase and catalase) and the level of lipid peroxidation. The neurobehavioural alteration in the treated mice was studied by the shuttle box method. Results: 232Th accumulation found in different brain regions followed the order: Cerebellum (Cbl) > cortex (Ctx) > hippocampus (Hp) > striatum (Str). However, removal of 232Th by Ca-DTPA was significant from brain regions like Cbl, Ctx and Str but not from Hp. A significant increase in lipid peroxidation and acetylcholine esterase (AChE) activity was observed in the treated mice but activities of superoxide dismutase and catalase was found substantially decreased. 232Th treatment impaired the learning and memory-based neurobehaviour of the mice. Furthermore, our data suggest that Ca-DTPA injection in 232Th-treated animals failed to improve the neurobehaviour of the treated mice, perhaps because Ca-DTPA could not decorporate 232Th or mitigate 232Th-mediated neurochemical changes effectively from/in hippocampus, a brain region implicated in learning and memory response. Conclusion: Administration of 232Th in mice caused neurobehavioural alteration and impairment of cholinergic function, which might be the consequence(s) of oxidative stress induction in different brain regions. [ABSTRACT FROM AUTHOR]

Purpose: Thorium (232Th, IV) preferentially accumulates in the liver, femur and spleen, which necessitates evaluation of its toxic effect in these organs. The present study was aimed at evaluation of liver function, oxidative stress and histological alterations in these organs. Materials and methods: Swiss albino mice were administered either with Thorium nitrate (10 mg/kg body weight/day equivalent to 1090 pCi/kg body weight/day) for 30 days (1/40th dose of LD50/30; the dose of thorium required to kill 50% of the test cohort within 30 days) intraperitoneally or with calcium salt of diethylenetriamine pentaacetate (Ca-DTPA, 100 μmole/kg body/weight) intravenously or both. Liver function tests and oxidative damage was assessed. The concentration of Th in the tissues was determined by Inductively Coupled Plasma-Atomic Emission Spectroscopy (ICP-AES) method. Results: Administration of Th prevented the increase in the body and liver weight and altered liver functions. Th treatment to mice showed a decrease in the activities and gene expression of antioxidant enzymes, and increased lipid peroxidation and protein carbonylation. The extent of observed oxidative damage was correlated with accumulation of Th in examined organs and further associated with histological alterations. Furthermore it was found that these effects were significantly lower when the chelating agent, Ca-DTPA, was given 1 h after Th injection. Conclusion: Administration of subtoxic concentration of Th to mice markedly altered the liver functions and induced oxidative stress in the liver, femur and spleen of mice. The results further demonstrated that Ca-DTPA significantly protected mice against the toxic effects of Th. [ABSTRACT FROM AUTHOR]

Introduction: Ischemia–reperfusion injury (IRI) is the inexplicable aggravation of cellular dysfunction that results in blood flow restoration to previously ischemic tissues. COX mediates the oxidative conversion of AA to various prostaglandins and thromboxanes, which are involved in various physiological and pathological processes. In the pathophysiology of I/R injuries, COX has been found to play an important role. I/R injuries affect most vital organs and are characterized by inflammation, oxidative stress, cell death, and apoptosis, leading to morbidity and mortality. Materials and methods: A systematic literature review of Bentham, Scopus, PubMed, Medline, and EMBASE (Elsevier) databases was carried out to understand the Nature and mechanistic interventions of the Cyclooxygenase modulations in ischemic injury. Here, we have discussed the COX Physiology and downstream signalling pathways modulated by COX, e.g., Camp Pathway, Peroxisome Proliferator-Activated Receptor Activity, NF-kB Signalling, PI3K/Akt Signalling in ischemic injury. Conclusion: This review will discuss the various COX types, specifically COX-1 and COX-2, which are involved in developing I/R injury in organs such as the brain, spinal cord, heart, kidney, liver, and intestine. [ABSTRACT FROM AUTHOR]

The present study evaluated the effect of coenzyme Q10 nanoparticles (CoQ NPs) against monocrotophos (MCP) exposure-induced oxidative stress in kidney tissue of rats. Albino wistar rats were divided into four groups i.e. control, CoQ NPs-treated, MCP-treated and MCP + CoQ NPs-treated groups. An acute dose of MCP (4.5 mg/kg b.wt) dissolved in corn oil was administered while CoQ NPs were given at a dose of 100 mg/kg b.wt 2 h before MCP treatment. Results showed that MCP exposure resulted in oxidative stress generation in kidney tissue of rats as depicted by increased lipid peroxidation and protein oxidation followed by decreased glutathione content in tissue homogenate. The activity of superoxide dismutase also decreased significantly in kidney tissue. Histopathological analysis showed many cellular alterations in the kidney tissue supporting the toxic effects of MCP exposure in rats. Co-treatment of CoQ NPs with MCP significantly ameliorated the oxidative stress generation and improved the histological alterations. The results indicate that CoQ NPs have the potential to reverse the oxidative stress generated after MCP exposure in rat kidneys suggesting their therapeutic potential. [ABSTRACT FROM AUTHOR]

[Display omitted] • Systemic oxidative stress and inflammation are significant outcomes of SARS-CoV-2 infection. • Activated Gsk-3 following SARS-CoV-2 infection provoke the oxidative stress and inflammation in the host. • Gsk-3 phosphorylates nucleocapsid protein of SARS-CoV-2 and helps in disease progression. • Inhibition of Gsk-3 can be a suitable target in curbing of COVID-19 pandemic. The coronavirus disease 19 (COVID-19) outbreak caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) had turned out to be highly pathogenic and transmittable. Researchers throughout the globe are still struggling to understand this strain's aggressiveness in search of putative therapies for its control. Crosstalk between oxidative stress and systemic inflammation seems to support the progression of the infection. Glycogen synthase kinase-3 (Gsk-3) is a conserved serine/threonine kinase that mainly participates in cell proliferation, development, stress, and inflammation in humans. Nucleocapsid protein of SARS-CoV-2 is an important structural protein responsible for viral replication and interferes with the host defence mechanism by the help of Gsk-3 protein. The viral infected cells show activated Gsk-3 protein that degrades the Nuclear factor erythroid 2-related factor (Nrf2) protein, resulting in excessive oxidative stress. Activated Gsk-3 also modulates CREB-DNA activity, phosphorylates NF-​κB, and degrades β-catenin, thus provokes systemic inflammation. Interaction between these two pathophysiological events, oxidative stress, and inflammation enhance mucous secretion, coagulation cascade, and hypoxia, which ultimately leads to multiple organs failure, resulting in the death of the infected patient. The present review aims to highlight the pathogenic role of Gsk-3 in viral replication, initiation of oxidative stress, and inflammation during SARS-CoV-2 infection. The review also summarizes the potential Gsk-3 pathway modulators as putative therapeutic interventions in combating the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Abstract: The present study investigates the potential of Carnosine, a histamine precursor in rat model of bilateral common carotid artery occlusion (BCCAo)‐induced vascular dementia (VaD). Wistar rats were subjected to BCCAo procedure under anaesthesia to induce VaD. The rats were subjected to Morris water maze (MWM) test (6th day onwards post‐surgery). MWM test was employed to assess learning and memory of the animals whereby escape latency time, time spent in target quadrant and Path length (distance travelled) taken as important parameters. Serum nitrite level; Brain thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) levels; Brain acetylcholinesterase (AChE) activity; brain Myeloperoxidase activity (MPO) and neutrophil count were estimated as per standard procedures. BCCAo in rats produced a significant vascular endothelial dysfunction, as reflected by decrease in serum nitrite levels. Further, these animals showed poor performance on MWM, depicting impairment of learning and memory. There was a significant rise in brain oxidative stress level as indicated by increase in TBARS and decrease in GSH levels. An increase in brain AChE activity was also observed. Moreover, these rats also exhibited an increase in MPO activity and neutrophil infiltration in brain (as marker of inflammation). Treatment of Carnosine (200 and 400 mg/kg, i.p.)/Donepezil (0.3 mg/kg, i.p.) ameliorated BCCAo‐induced memory deficits; endothelial dysfunction; biochemical and histopathological changes. It is concluded that Carnosine has shown efficacy in rat model of BCCAo‐induced VaD and can be considered as an important therapeutic agent for the treatment of VaD. [ABSTRACT FROM AUTHOR]

Obesity is associated with severe, difficult-to-control asthma, and increased airway oxidative stress. Mitochondrial reactive oxygen species (mROS) are an important source of oxidative stress in asthma, leading us to hypothesize that targeting mROS in obese allergic asthma might be an effective treatment. Using a mouse model of house dust mite (HDM)-induced allergic airway disease in mice fed a low- (LFD) or high-fat diet (HFD), and the mitochondrial antioxidant MitoQuinone (MitoQ), we investigated the effects of obesity and ROS on HDM-induced airway inflammation, remodeling, and airway hyperresponsiveness (AHR). Obese allergic mice showed increased lung tissue eotaxin, airway tissue eosinophilia, and AHR compared with lean allergic mice. MitoQ reduced airway inflammation, remodeling, and hyperreactivity in both lean and obese allergic mice, and tissue eosinophilia in obese-allergic mice. Similar effects were observed with decyl triphosphonium (dTPP+), the hydrophobic cationic moiety of MitoQ lacking ubiquinone. HDM-induced oxidative sulfenylation of proteins was increased particularly in HFD mice. Although only MitoQ reduced sulfenylation of proteins involved in protein folding in the endoplasmic reticulum (ER), ER stress was attenuated by both MitoQ and dTPP+ suggesting the anti-allergic effects of MitoQ are mediated in part by effects of its hydrophobic dTPP+ moiety reducing ER stress. In summary, oxidative signaling is an important mediator of allergic airway disease. MitoQ, likely through reducing protein oxidation and affecting the UPR pathway, might be effective for the treatment of asthma and specific features of obese asthma. [ABSTRACT FROM AUTHOR]

CYP2E1 plays a crucial role in the bio-activation of toxic substances leading to liver damage. In this context, CYP2E1 converts paracetamol (PCM) to N-acetyl-p-benzoquinone imine (NAPQI), which is prone to cause hepatotoxicity. Hence, we aimed to explore the protective effect of glabridin on widely used PCM-induced liver injury model in the present study and, after that, correlated with the role of CYP2E1 toward its efficacy. Glabridin was isolated from Glycyrrhiza glabra and characterized before the investigation in an in-vivo mice model of PCM-induced liver injury. Glabridin after oral treatment at 5–20 mg/kg showed a considerable improvement in serum biochemical parameters (ALT and AST) and oxidative stress markers (MDA, GSH, SOD, and catalase) in comparison to only PCM-treatment. Histopathological examination of the liver depicted that glabridin exhibited substantial protection from PCM-induced liver injury compared to the disease control group. Significant down-regulation of CYP2E1 protein and its mRNA expression levels were observed in the glabridin-treated groups compared to PCM-induced respective elevation of CYP2E1. Moreover, activation of NF-κB was significantly inhibited by glabridin. Therefore, glabridin has the potential to protect PCM-induced liver injury through CYP2E1 inhibition-mediated normalization of oxidative stress. Further research is warranted to establish glabridin as a phytotherapeutics for liver protection for which no effective and safe oral drug is available to date. [ABSTRACT FROM AUTHOR]

Sperm mitochondrion is one of the major susceptible organelles that get damaged during cryopreservation. The study aimed to minimize mitochondrial dysfunction and oxidative stress during sperm cryopreservation using mitochondria‐specific antioxidants. For this, semen was collected from five buffalo bulls (3 ejaculates/bull). The ejaculates were diluted in an low‐density lipoprotein‐based extender and divided into four equal aliquots. Mitochondria‐targeted antioxidant (MitoQ) was added at a final concentration of 0 (control), 0.02, 0.2 and 2 μM separately in each aliquotes and cryopreserved. The addition of MitoQ at a concentration of 0.02 μM improved post‐thaw sperm motility, plasma membrane integrity and able to sustain sperm motility for a longer time. To investigate MitoQ's effects on mitochondrial function, we measured mitochondrial membrane potential (MMP) using JC‐1 dye, superoxide production using Mitosox assay, and lipid peroxidation by TBARS assay. The supplementation of 0.02 μM MitoQ in the extender prevented the significant reduction of MMP and reduced superoxide production resulting in lower lipid peroxidation of sperm plasma membrane after cryopreservation. Further, we found that a higher concentration of MitoQ decreases MMP and increases mitochondrial superoxide production. In conclusion, MitoQ @ 0.02 μM can alleviate oxidative stress by regulating mitochondrial functionality in spermatozoa during cryopreservation. [ABSTRACT FROM AUTHOR]

The risk of neurodegeneration was found to be increased among people with type 2 diabetes mellitus (T2DM). Brain disorders like Alzheimer's disease, Parkinson's disease, Huntington's disease, Amyotrophic lateral sclerosis, and others are considered neurodegenerative diseases and can be characterized by progressive loss of neurons. The deficiency of insulin, impaired signaling, and its resistance lead to alteration in the neuronal functioning of the brain. Insulin degrading enzyme (IDE) plays a significant role in the amyloid β metabolism, aggregation, and deposition of misfolded proteins in the brain's hippocampal and cortical neuronal regions. The insulin signaling via IP3 activation upregulates the IDE and could be a promising approach to regulate neurodegeneration. The repurposing of existing antidiabetic drugs such as Metformin, DPP-4 inhibitors, thiazolidinediones, glucagon-like peptides (GLP-1), sodium-glucose co-transport-2 (SGCT-2) inhibitors, and insulin could be an alternative and effective strategy to treat neurodegeneration via modulating insulin signaling, insulin resistance, IDE activity, oxidative stress, mitochondrial dysfunction, serum lipid profile and neuroinflammation in the brain. Antidiabetic medications reduce the risk of neuroinflammation, oxidative stress, and Aβ deposition by enhancing their clearance rate. The downregulation of IDE alters the degradation of Aβ monomers in the Tg2576 APP mice. Also, the treatment with metformin activated the AMPK pathway and suppressed mTOR and BACE-1 protein expression in the APP/PS1-induced mice model. Thus, the primary intention of this review is to explore the link between T2DM and neurodegenerative disorders, and the possible role of various antidiabetic drugs in the management of neurodegenerative disorders. [Display omitted] [ABSTRACT FROM AUTHOR]

Present investigation was carried out to determine the effect of calf weaning and natural suckling on the growth performance, immune status, health and behaviour of buffalo calves. Sixteen newly born calves (8 calves from weaned group and 8 calves from natural suckling group) were raised in two separate groups under loose housing system. The mean daily colostrum intake during first two days was higher in suckled calves as compared to weaned calves. The average daily body weight gain was significantly higher (0.506 vs. 0.438 kg/day) in suckled calves as compared to weaned calves. The mean of time spent on cross sucking, licking self and licking objects were significantly higher in weaned calves as compared to suckled calves. The level of oxidative stress of weaned calves were significantly higher as compared to suckled calves. It was concluded that the growth performance, immune status, health, behaviour and oxidative stress of natural suckled calves were better as compared to that of weaned calves. [ABSTRACT FROM AUTHOR]

Abstract: Rapid and effective wound healing requires a coordinated cellular response involving fibroblasts, keratinocytes and vascular endothelial cells (VECs). Impaired wound healing can result in multiple adverse health outcomes and, although antibiotics can forestall infection, treatments that accelerate wound healing are lacking. We now report that topical application of water soluble cerium oxide nanoparticles (Nanoceria) accelerates the healing of full-thickness dermal wounds in mice by a mechanism that involves enhancement of the proliferation and migration of fibroblasts, keratinocytes and VECs. The Nanoceria penetrated into the wound tissue and reduced oxidative damage to cellular membranes and proteins, suggesting a therapeutic potential for topical treatment of wounds with antioxidant nanoparticles. [Copyright &y& Elsevier]

Abstract: Cerium oxide nanoparticles (CeNPs) have shown promise as catalytic antioxidants in cell culture and animal models as both superoxide dismutase and catalase mimetics. The reactivity of the cerium (Ce) atoms at the surface of its oxide particle is critical to such therapeutic properties, yet little is known about the potential for a protein or small molecule corona to form on these materials in vivo. Moreover Ce atoms in these active sites have the potential to interact with small molecule anions, peptides, or sugars when administered in culture or animal models. Several nanomaterials have been shown to alter or aggregate under these conditions, rendering them less useful for biomedical applications. In this work we have studied the change in catalytic properties of CeNPs when exposed to various biologically relevant conditions in vitro. We have found that CeNPs are resistant to broad changes in pH and also not altered by incubation in cell culture medium. However to our surprise phosphate anions significantly altered the characteristics of these nanomaterials and shifted the catalytic behavior due to the binding of phosphate anions to cerium. Given the abundance of phosphate in biological systems in an inorganic form, it is likely that the action of CeNPs as a catalyst may be strongly influenced by the local concentration of phosphate in the cells and/or tissues in which it has been introduced. [Copyright &y& Elsevier]

Nrf2-mediated activation of antioxidant response element is a central part of molecular mechanisms governing the protective function of phase II detoxification and antioxidant enzymes against carcinogenesis, oxidative stress, and inflammation. Nrf2 is sequestered in the cytoplasm by its repressor, Keap1. We have designed and synthesized novel chalcone derivatives as Nrf2 activators. The potency of these compounds was measured by the expression of Nrf2 dependent antioxidant genes GCLM, NQO1, and HO1 in human lung epithelial cells, while the cytotoxicity was analyzed using MTT assay. In vivo potency of identified lead compounds to activate Nrf2 was evaluated using a mouse model. Our studies showed 2-trifluoromethyl-2′-methoxychalone (2b) to be a potent activator of Nrf2, both in vitro and in mice. Additional experiments showed that the activation of Nrf2 by this compound is independent of reactive oxygen species or redox changes. We have discussed a quantitative structure–activity relationship and proposed a possible mechanism of Nrf2 activation. [ABSTRACT FROM AUTHOR]

Despite unprecedented advances in modern medicine, no safe and effective drug is available to date for oral administration to combat drug-induced liver injury, which is a vital concern nowadays. The present study deals with the hepatoprotective effect of pure glabridin, a key phytoconstituent from Glycyrrhiza glabra with mechanistic investigations using an in-vivo methotrexate-induced liver injury model as there is no such precedent. The study was performed in the Swiss mice model where a single dose of methotrexate (40 mg/kg) was given on the 7th day through an intraperitoneal route to induce hepatotoxicity, and glabridin as a test compound was administered orally for eleven consecutive days at 10 to 40 mg/kg. Glabridin markedly improved serum biochemical parameters (SGPT, SGOT), proinflammatory cytokine (TNF-α) level, oxidative stress markers (MDA, GSH, SOD, CAT) as compared to methotrexate alone. Alterations in methotrexate-induced liver architecture were considerably prevented by glabridin treatment as suggested by liver histopathological examination and SEM investigation. Glabridin substantially prevented methotrexate-induced down-regulation of Nrf2, & activation of NF-κB, and caused up-regulation of BAX at different dose levels. Overall, glabridin is found to protect methotrexate-induced hepatotoxicity by improving important factors for oxidative stress, inflammation, and apoptosis. • Glabridin attenuates oxidative stress during methotrexate-induced liver injury. • Glabridin regulates inflammation and apoptosis to improve hepatotoxicity. • Glabridin have potential to be phytotherapeutics for liver protection. [ABSTRACT FROM AUTHOR]

Skin aging is caused by exposure to various external factors. Ultraviolet B (UVB) irradiation induces oxidative stress, photoaging, and inflammation in skin cells. Pinus densiflora Sieb. et Zucc. (red pine) has various antimicrobial and antioxidant activities. However, the anti-inflammatory effects of red pine on skin have rarely been reported. The protective effects of malonic acid (MA) isolated from Pinus densiflora were investigated against UVB-induced damage in an immortalized human keratinocyte cell line (HaCaT). MA increased levels of the antioxidant enzymes superoxide dismutase 1 (SOD-1) and heme oxygenase 1 (HO-1) via activation of nuclear factor-erythroid 2-related factor-2 (Nrf2), resulting in a reduction in UVB-induced reactive oxygen species (ROS) levels. Additionally, the inhibition of ROS increased HaCaT cell survival rate. Thus, MA downregulated the expression of ROS-induced nuclear factor-κB, as well as inflammation-related cytokines (interleukin-6, cyclooxygenase-2, and tumor necrosis factor-α). Furthermore, MA significantly suppressed the mitogen-activated protein kinase/activator protein 1 signaling pathway and reduced the expression of matrix metalloproteinases (MMPs; MMP-1, MMP-3, and MMP-9). In contrast, MA treatment increased the expression of collagen synthesis regulatory genes (COL1A1 and COL3A1) via regulation of Smad2/3 signal induction through transforming growth factor-β. In conclusion, MA protected against UVB-induced photoaging via suppression of skin inflammation and induction of collagen biosynthesis. [ABSTRACT FROM AUTHOR]