Search

Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint inflammation driven by complex signaling pathways. Recent therapeutic approaches focus on small molecules targeting intracellular signaling to address specific physiological aspects of the disease. Previously we identified a small molecule, 2-hydroxyestradiol (2-OHE2), an inhibitor of TNF-α by an in-silico study. In the present study, our aim was to explore the efficacy of 2-OHE2 by studying the proteome profile of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) using SWATH-MS and validate its therapeutic potential in RA by in-vitro studies. Oxidative stress was assessed using various biochemical assays, and cellular bioenergetics were analyzed with the Seahorse XFe96 Analyzer. We identified 396 differential proteins by SWATH-MS, and 82 showed significant changes. PharmMapper analysis revealed the association of 2-OHE2 with HMOX1 (HO-1), confirmed by SWATH-MS data. Also, we revealed that 2-OHE2 enhanced the expression of HO-1 and lowered oxidative stress via activating the Nrf2/KEAP1/HO-1 pathway. Further, 2-OHE2 has been found to boost cellular respiration and ATP production. Our findings thus suggest that 2-OHE2 possesses therapeutic potential as an antioxidant for RA treatment, effective at low dosages., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The pattern of copper (Cu) toxicity in humans is similar to Wilson disease, and they have movement disorders and frequent involvement of corpus striatum. The extent of cell deaths in corpus striatum may be the basis of movement disorder and may be confirmed in the experimental study. To evaluate the extent of apoptosis and glial activation in corpus striatum following Cu toxicity in a rat model, and correlate these with spontaneous locomotor activity (SLA), six male Wistar rats were fed normal saline (group I) and another six were fed copper sulfate 100 mg/kgBWt/daily orally (group II). At 1 month, neurobehavioral studies including SLA, rotarod, and grip strength were done. Corpus striatum was removed and was subjected to glial fibrillary acidic protein (GFAP) and caspase-3 immunohistochemistry. The concentration of tissue Cu, total antioxidant capacity (TAC), glutathione (GSH), malondialdehyde (MDA), and glutamate were measured. Group II rats had higher expression of caspase-3 (Mean ± SEM 32.67 ± 1.46 vs 4.47 ± 1.08; p < 0.01) and GFAP (41.81 ± 1.68 vs 31.82 ± 1.27; p < 0.01) compared with group I. Neurobehavioral studies revealed reduced total distance traveled, time moving, the number of rearing, latency to fall on the rotarod, grip strength, and increased resting time compared with group I. The expression of GFAP and caspase-3 correlated with SLA parameters, tissue Cu, GSH, MDA, TAC, and glutamate levels. The impaired locomotor activity in Cu toxicity rats is due to apoptotic and inflammatory-mediated cell death in the corpus striatum because of Cu-mediated oxidative stress and excitotoxicity.

Food and feeds contaminated with mycotoxins have been a threat to the rearing industry by causing some of the most fatal toxic reactions not only in the farm animals but also in humans who consume them. Toxicity to juvenile goats was induced by feed contamination with T-2 toxin (at 10 and 20 ppm dosage; group I and II, respectively). The toxicity impact was assessed on days 15 and 30 post treatment with respect to growth performance, oxidative stress, apoptotic studies and detailed pathomorphology. The study revealed that apart from the obvious clinical toxicosis (weakness, lethargy, and retardation in growth), the toxin fed groups also exhibited significant haematological (reduced hemoglobin, total leukocyte and thrombocyte counts) and biochemical changes (increased levels of oxidative stress markers with concomitant decrease in levels of serum and tissue catalase and superoxide dismutase). The pathomorphological and histological alterations suggested that the liver and intestine were the most affected organs. Ultra-structurally, varying degrees of degeneration, cytoplasmic vacuolations and pleomorphic mitochondria were observed in the hepatocytes and the enterocytes of the intestine. Kidney also revealed extensive degeneration of the cytoplasmic organelles with similar condensation of the heterochromatin whereas the neuronal degeneration was characterized by circular, whirling structures. In addition, the central vein and portal triad of the hepatocytes, cryptic epithelial cells of the intestine, MLNs in the lymphoid follicles, PCT and DCT of the nephronal tissues and the white pulp of the spleen exhibited extensive apoptosis. In this study, it was also observed that the expression of HSPs, pro-apoptotic proteins and pro-inflammatory cytokines were significantly upregulated in response to the toxin treatment. These results suggest that the pathogenesis of T-2 toxicosis in goats employs oxidative, apoptotic and inflammatory mechanisms., Competing Interests: The authors have declared that no competing interests exist.

Anti-inflammatory drugs are well known to reduce the risk of colon cancer and prophylactic use of such agents is gaining acceptance as a cancer prevention therapy. As artesunate, an antimalarial drug, has been shown to exhibit chemopreventive properties, the present study was carried out to evaluate its inhibitory effect on oxidative stress and inflammation in a rat model of colon carcinogenesis. A chemical carcinogen, 1,2-dimethylhydrazine was injected twice at an interval of 1 week to induce preneoplastic lesions in the colon and the parameters indicating oxidative stress and inflammation were evaluated after 8 weeks. Artesunate (50 and 150 mg/kg) and aspirin (60 mg/kg) were administered orally throughout the study. Analysis of colon tissue revealed that both the drugs preserved histoarchitecture, inhibited cellular influx, decreased the levels of oxidative stress and inflammatory markers, downregulated cyclooxygenase-2, inducible nitric oxide synthase, nuclear factor κB, and interleukin 1β in comparison to the experimental control. Suppression of oxidative stress and pro-inflammatory signaling by both the drugs were found to contribute to inhibition of colon carcinogenesis. The protection afforded by these drugs was found to be comparable. Our study shows that like aspirin, use of artesunate could also reduce the risk of colon cancer and it has a potential for further evaluation for the treatment purpose., (© 2019 Wiley Periodicals, Inc.)

Calotropis procera, a latex producing plant is known to possess medicinal properties including its beneficial effect in gastrointestinal disorders. The anti-inflammatory effect of its latex in various experimental models is noteworthy and in light of this the present study was carried out with an objective to evaluate its efficacy in ulcerative colitis, an inflammatory condition of the colon. Colitis was induced in rats by acetic acid and the rats were divided into four groups where one group served as experimental control and the other groups were treated with two doses of methanol extract of dried latex of C. procera (MeDL; 50 and 150 mg/kg) and mesalazine (MSZ; 300 mg/kg). The study also included normal control (NC) group for comparison of various parameters related to colon like macroscopic changes, ulcer score, adherent mucus content, weight/length ratio, small intestinal transit, oxidative stress and inflammatory markers, tissue histology and immunoreactivity of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) and nuclear factor kappa beta (NFκB) subunit p65. Treatment of colitic rats with MeDL produced a significant reduction in colonic mucosal damage as revealed by macroscopic and microscopic evaluation and normalization of tissue levels of oxidative stress markers and pro-inflammatory mediators. The protection afforded by MeDL was also evident from its restorative effect on tissue histology and expression of COX-2, iNOS and NFκB(p65). This study shows that by targeting oxidative stress and NFκB(p65) mediated pro-inflammatory signaling, the latex of C. procera affords protection in colitis and its effect was comparable to that of mesalazine. This study suggests that latex of C. procera could serve as a promising therapeutic option for treating inflammatory conditions of the colon., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

The present study was designed to evaluate the ameliorative effect of ethyl acetate extract of Premna integrifolia L. (EAEPI) leaves in cyclophosphamide (CP)-induced hepatic injury in mice. Mice were intoxicated with CP (200 mg/kg b. wt., i.p.) for 5 weeks or EAEPI (400 and 600 mg/kg b. wt., orally) in combination with CP. The results demonstrated that EAEPI exerts protective effect against CP induced hepatotoxicity, as evident from restoration of altered haematological parameters and alleviations of liver marker enzymes in serum. EAEPI also attenuated oxidative stress and antioxidant markers as evident from reversal of lipid peroxidation, glutathione levels as well as activities of catalase and superoxide dismutase enzymes. Moreover, EAEPI attenuated apoptosis and histopathological liver tissue damage in CP-intoxicated mice. In conclusion, EAEPI could protect mice liver against cyclophosphamide toxicity by inhibiting oxidative stress and apoptosis.The protective activity of EAEPI may be due to presence of polyphenolic compounds as identified by UHPLC-Q-TOF-MS/MS., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

The present study reports beneficial effect of hydroxytyrosol (HT) against arsenic (As)-induced oxidative stress in the rat brain. Rats were orally administered with sodium arsenite dissolved in distilled water (25 ppm, by oral gavage) for 8 weeks or HT (10 mg/kg b. wt.) in combination with As. Results showed increase in protein oxidation and lipid peroxidation, while catalase and superoxide dismutase (SOD) activities as well as GSH content were decreased after As exposure in rat brain. Fourier transform infrared analysis showed significant alteration in peak area values that also validated the oxidative damage to lipids and proteins. In addition, As exposure caused increase in protein expression of caspase-3 and Bax, while Bcl-2 expression was downregulated resulting in translocation of cytochrome c from mitochondria to cytosol. Treatment of HT with As reversed protein oxidation, lipid peroxidation, and increased GSH content as well as catalase and SOD activities. Administration of HT also prevented translocation of cytochrome c from mitochondria and increased mitochondria/cytosol ratio of cytochrome c. Hence, treatment of HT with As improved antioxidant system and efficiently lowered the generation of oxidative stress in rat brain.

The prototype disease of Cu toxicity in human is Wilson disease, and cognitive impairment is the presenting symptom of it. There is no study correlating Cu-induced excitotoxicity, apoptosis, and astrocytic reaction with memory dysfunction. We report excitotoxicity, apoptosis, and astrocytic reaction of the hippocampus and frontal cortex with memory dysfunction in rat model of Cu toxicity. Thirty-six rats were divided into group I (control) and group II (100 mg/kgBwt/day CuSO 4 orally). Y-maze was performed for memory and learning at 0, 30, 60, and 90 days. Frontal and hippocampal free Cu concentration, oxidative stress markers [glutathione (GSH), total antioxidant toxicity (TAC), and malondialdehyde (MDA)], and glutamate were measured by atomic absorption spectroscopy, spectrophotometry, and ELISA, respectively. N-methyl-D-aspartate receptors (NMDARs) NR1, NR2A, and NR2B were done by real-time polymerase chain reaction. Immunohistochemistry for caspase-3 and glial fibrillary acidic protein (GFAP) were done and quantified using the ImageJ software. The glutamate level in hippocampus was increased, and NMDAR expression was decreased at 30, 60, and 90 days in group II compared to group I. In the frontal cortex, glutamate was increased at 90 days, but NMDARs were not significantly different in group II compared to group I. Caspase-3 and GFAP expressions were also higher in group II compared to group I, and these changes were more marked in hippocampus than frontal cortex. These changes correlated with respective free tissue Cu, oxidative stress, and Y-maze attention score. Cu toxicity induces apoptosis and astrocytosis of the hippocampus and frontal cortex through direct or glutamate and oxidative stress pathways, and results in impaired memory and learning.

Background: Prolonged use of aspirin, a commonly prescribed non steroidal anti-inflammatory drug, is well known to produce gastrointestinal toxicity which could be minimized by various anti-secretory agents. The present study was carried out to evaluate the protective effect of artesunate against aspirin induced gastric injury in rats., Methods: Gastric injury was induced in fasted Wistar rats by oral administration of aspirin. The effect of 50 and 150mg/kg of artesunate was studied on macroscopic changes, gastric secretions, histology, oxidative stress and inflammatory markers in the stomach tissue after 5h of induction of gastric injury. Immunohistochemical analysis for the expression of IL-1β, IL-6, NF-κB(p65) and COX-2 was also carried out. The effect of artesunate was compared with that of standard anti-ulcer drug famotidine (20mg/kg)., Results: Artesunate pretreatment produced a dose-dependent reduction in aspirin induced gastric injury and restored the gastric juice parameters. It normalized the tissue levels of oxidative stress markers (glutathione, malondialdehyde and superoxide dismutase activity) and mediators of inflammation (myeloperoxidase and TNF-α). The protection afforded by artesunate was evident from the histoarchitecture of stomach tissue and marked reduction in tissue expression of IL-1β, IL-6, NF-κB(p65) and COX-2. The effect of artesunate was found to be comparable to that of standard drug famotidine., Conclusion: Artesunate markedly ameliorated aspirin induced gastric injury in rats by targeting oxidative stress and COX-2 dependent as well as COX-2 independent proinflammatory signaling pathways and could have a therapeutic potential in gastric ulcer disease., (Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.)

Objective and Design: Roxithromycin, a macrolide antibiotic, exhibits anti-inflammatory property. The present study was designed to evaluate its protective effect in a rat model of colitis., Methods: The anti-inflammatory property of roxithromycin was first validated in rat paw edema model at 5 and 20 mg/kg doses where it produced 19 and 51% inhibition of paw swelling induced by carrageenan. The efficacy of roxithromycin was evaluated at these doses in a rat model where colitis was induced by intra-colonic instillation of acetic acid. Rats were divided into six groups viz. normal control, experimental control and drug-treated groups: roxithromycin 5 and 20 mg/kg, diclofenac 10 mg/kg and mesalazine 300 mg/kg. All drugs were given orally 1 h before induction of colitis. The macro and microscopic changes, mean ulcer score, mucus content and markers of oxidative stress and inflammation were evaluated in all the groups after 24 h., Results: Pretreatment with roxithromycin markedly decreased hyperemia, ulceration, edema and restored histological architecture. The protection afforded by roxithromycin was substantiated by dose-dependent increase in mucus content, normalization of markers of oxidative stress (GSH and TBARS) and levels of TNF-α, PGE 2 and nitrite along with marked decrease in expression of NFκB (p65), IL-1β and COX-2. The protective effect of roxithromycin was found to be comparable to mesalazine while diclofenac was found ineffective., Conclusion: Our study demonstrates that roxithromycin ameliorates experimental colitis by maintaining redox homeostasis, preserving mucosal integrity and downregulating NFκB-mediated pro-inflammatory signaling and suggests that it has a therapeutic potential in inflammatory conditions of the colon.

The first committed step of the shikimate pathway is catalyzed by a metalloenzyme 3-deoxy-d-arabino-heptulosonate-7-phosphate synthase (DAH7PS), which exhibits vulnerability to the oxidative stress. DAH7PS undergoes inactivation in multiple ways in the presence of redox metal, H 2 O 2 , and superoxide. The molecular mechanism and susceptibility of its inactivation might differ in different organisms and are presently unclear. In the present work, we have cloned, expressed and purified a DAH7PS from Providencia alcalifaciens (PaDAH7PS). The oligomeric state and effect of redox metal treatment on its stability were analyzed through the size exclusion chromatography. The FTIR, MALDI-TOF/TOF-MS studies revealed that methionine residues were modified to methionine sulfoxide in PaDAH7PS. During oxidation, PaDAH7PS is altered into partially folded protein and unfolded states as determined by CD and Fluorescence studies. A significant loss in enzymatic activity of PaDAH7PS was determined and the formation of amorphous aggregates was visualized using AFM imaging and also confirmed by ThT binding based assay. This is the first report where we have shown a hexameric DAH7PS and the methionine residues of PaDAH7PS get oxidize in the presence of oxidative stress. The partially folded and unfolded oligomeric states with high β-content of PaDAH7PS might be the critical precursors for aggregation., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Metformin, an antidiabetic drug, is well known for its multifarious properties and its ability to modulate inflammatory cascade. Ulcerative colitis (UC) is an inflammatory condition of the colon where drugs exhibiting anti-inflammatory property have been shown to induce and maintain remission. The objective of the present study was to evaluate the efficacy of metformin against acetic-acid induced colitis in rat. The study included five groups of rats namely normal control, experimental control, drug treated groups (50 and 500mg/kg of metformin, MET50, MET500 and 300mg/kg of mesalazine, MSZ300). Parameters like small intestinal transit and colonic macroscopic changes, ulcer score, weight/length (W/L) ratio, levels of oxidative stress and inflammatory markers, tissue histology and expression of COX-2, iNOS, NFκB(p65) were evaluated. The results of this study show that treatment with metformin significantly decreased colonic mucosal damage, maintained oxidative homeostasis and normalized intestinal transit and W/L ratio in a dose-dependent manner. The restorative effect of metformin on colonic mucosa was accompanied by a marked reduction in the tissue levels of pro-inflammatory mediators and immunoreactivity of COX-2, iNOS and NFκB(p65). Further, its protective effect was found to be comparable to that of mesalazine. This study shows that metformin targets oxidative stress and down regulates transcription factor NFκB(p65) mediated pro-inflammatory signaling and has a therapeutic potential in treating inflammatory conditions of the colon., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

A number of factors like alcohol consumption, stress, use of non steroidal anti-inflammatory drugs and acidity are well known to increase the risk of development of gastric ulcers. The present study was carried out to investigate the protective effect of artesunate against gastric injury induced in rats by oral administration of ethanol and by pylorus ligation in independent sets of experiments. The groups included in each set (n = 6 per group) were normal control, experimental control and drug treated groups: artesunate 50 and 150 mg/kg (ART 50 and ART 150) and famotidine 20 mg/kg (FAM 20). Artesunate and famotidine were given orally 1 h before induction of gastric ulceration and the macroscopic changes, median ulcer score, gastric juice parameters (volume, pH and acidity), markers of oxidative stress and inflammation (GSH, SOD, TBARS and MPO) and tissue histology were evaluated in both the models. The study was extended further for determination of tissue levels of TNF-α and expression of IL-1β, IL-6 and NFκB (p65) in ethanol induced gastric ulcer model. The results of the present study show that pretreatment with artesunate significantly decreased hemorrhagic lesions and mucosal damage with marked reduction in median ulcer score in both the models. The protective effect of artesunate was concomitant with dose-dependent normalization of gastric juice parameters, markers of oxidative stress and lipid peroxidation. The ameliorative effect of artesunate was also supported by restoration of histological architecture. Furthermore, artesunate pretreatment also alleviated the gastric mucosal inflammation as revealed by significant decrease in the tissue level of pro-inflammatory cytokine TNF-α (p < 0.01) and tissue expression of IL-1β, IL-6 and NFκB (p65). The protective effect of artesunate was found to be comparable to that of famotidine. Conclusively, artesunate afforded significant gastroprotection in rat due to its anti-oxidant and anti-inflammatory properties with transcription factor NFκB(p65) and its downstream inflammatory cascade as a plausible target for its action., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Preclinical Research The antidiabetic drug, metformin, can inhibit the release of inflammatory mediators in several disease conditions. The present study was carried out to evaluate the efficacy of metformin in ameliorating edema formation, oxidative stress, mediator release and vascular changes associated with acute inflammation in the rat carrageenan model. Metformin dose-dependently inhibited paw swelling induced by carrageenan and normalized the tissue levels of the inflammatory markers myeloperoxidase and nitrite. It also maintained oxidative homeostasis as indicated by near normal levels of the oxidative stress markers glutathione, thiobarbituric acid reactive substances, catalase and superoxide dismutase. The histopathology of the paw tissue in metformin-treated animals was similar to that in normal paw and had similar effects to diclofenac. In a rat peritonitis model, metformin reduced vascular permeability and cellular infiltration. In conclusion, this study shows that metformin has a potential for use in treating various inflammatory conditions., (© 2016 Wiley Periodicals, Inc.)

The present study was executed to study the effect of chronic arsenic exposure on generation of mitochondrial oxidative stress and biogenesis in rat liver. Chronic sodium arsenite treatment (25 ppm for 12 weeks) decreased mitochondrial complexes activity in rat liver. There was a decrease in mitochondrial superoxide dismutase (MnSOD) activity in arsenic-treated rats that might be responsible for increased protein and lipid oxidation as observed in our study. The messenger RNA (mRNA) expression of mitochondrial and nuclear-encoded subunits of complexes I (ND1 and ND2) and IV (COX I and COX IV) was downregulated in arsenic-treated rats only. The protein and mRNA expression of MnSOD was reduced suggesting increased mitochondrial oxidative damage after arsenic treatment. There was activation of Bax and caspase-3 followed by release of cytochrome c from mitochondria suggesting induction of apoptotic pathway under oxidative stress. The entire phenomenon was associated with decrease in mitochondrial biogenesis as evident by decreased protein and mRNA expression of nuclear respiratory factor 1 (NRF-1), nuclear respiratory factor 2 (NRF-2), peroxisome proliferator activator receptor gamma-coactivator 1α (PGC-1α), and mitochondrial transcription factor A (Tfam) in arsenic-treated rat liver. The results of the present study indicate that arsenic-induced mitochondrial oxidative stress is associated with decreased mitochondrial biogenesis in rat liver that may present one of the mechanisms for arsenic-induced hepatotoxicity.

The present study was carried out to investigate the molecular mechanism of arsenic-induced mitochondrial oxidative damage and its relation to biogenesis in rat brain. Chronic sodium arsenite (25 ppm, orally) administration for 12 weeks decreased mitochondrial complexes activities and mRNA expression of selective complexes subunits. The expression of mitochondrial biogenesis regulator PGC-1α, and its downstream targets NRF-1, NRF-2 and Tfam were decreased significantly both at mRNA and protein levels suggesting impaired biogenesis following chronic arsenic-exposure. In addition to this, protein expression analysis also revealed activation of Bax and caspase-3, leading to translocation of cytochrome c from mitochondria to cytosol suggesting induction of apoptotic pathway under oxidative stress. This was further confirmed by electron microscopy study which depicted morphological changes in mitochondria in terms of altered nuclear and mitochondrial shape and chromatin condensation in arsenic-treated rats. The immunohistochemical studies showed both nuclear and cytosolic localization of NRF-1 and NRF-2 in arsenic-exposed rat brain further suggesting regulatory role of these transcription factors under arsenic neurotoxicity. The results of present study indicate that arsenic-induced mitochondrial oxidative damage is associated with decreased mitochondrial biogenesis in rat brain that may present as important target to reveal the mechanism for arsenic-induced neurotoxicity., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Copper (Cu) at a higher level becomes toxic and it can catalyze the formation of highly reactive hydroxyl radical. We report the vulnerability of liver, kidney and brain to different dose of copper sulfate (CuSO4) induced oxidative stress at different time duration. Fifty-four male Wistar rats (weight range=205±10g) were equally divided into three groups. CuSO4 was administered orally to the experimental groups (Group-II and III) up to 90 days in a dose of 100 and 200mg/Kg body weight per day. Saline water was given to the control group (Group-I). At the end of 30, 60 and 90 days of administration, neurobehavioral studies were done and six rats from each group were sacrificed. Their liver, kidney and brain tissues were subjected for Cu, glutathione (GSH), malondialdehyde (MDA) and total antioxidant capacity (TAC) assay. Blood urea nitrogen (BUN), serum creatinine, bilirubin and transaminases were measured. GSH, TAC and MDA levels were correlated with the markers of respective organ dysfunction. Administration of CuSO4 resulted in increased free Cu and MDA level, and decrease GSH and TAC levels in group-II and III compared with group-I. In experimental groups, the reduction in TAC and GSH levels was maximum in liver tissue followed by brain and kidney; whereas increase in MDA level was highest in liver followed by brain and kidney at 30, 60 and 90 days. TAC and GSH levels in the liver inversely correlated with serum transaminases and bilirubin, and tissue free Cu, and positively correlated with MDA levels. Free Cu level in kidney tissue and BUN inversely correlated with TAC and GSH, and positively with MDA level. Grip-strength, rotarod and Y-maze findings were inversely correlated with brain free Cu and MDA levels and positively with GSH and TAC levels. The oxidative stress was highest in liver followed by brain and kidney after oral CuSO4 exposure in a rat model. These levels correlated with the respective organ dysfunction and tissue free Cu concentration., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Arsenic is a toxic metalloid present ubiquitously on earth. Since the last decade, it has gained considerable attention due to its severe neurotoxic effects. Arsenic can cross the blood-brain barrier and accumulate in different regions of the brain suggesting its role in neurological diseases. Arsenic exposure has been associated with reactive oxygen species generation, which is supposed to be one of the mechanisms of arsenic-induced oxidative stress. Mitochondria, being the major source of reactive oxygen species generation may present an important target of arsenic toxicity. It is speculated that the proper functioning of the brain depends largely on efficient mitochondrial functions. Multiple studies have reported evidence of brain mitochondrial impairment after arsenic exposure. In this review, we have evaluated the proposed mechanisms of arsenic-induced mitochondrial oxidative stress and dysfunction. The understanding of molecular mechanism of mitochondrial dysfunction may be helpful to develop therapeutic strategies against arsenic-induced neurotoxicity. The ameliorative measures undertaken in arsenic-induced mitochondrial dysfunction have also been highlighted., (Copyright © 2015 John Wiley & Sons, Ltd.)

Patients with neurologic Wilson disease (NWD) may worsen on treatment, but there is no study evaluating the role of oxidative stress. We report the role of plasma glutathione (GSH), total antioxidant capacity (TAC) and malondialdehyde (MDA) in the worsening of NWD following treatment. Fifty-one treatment-naïve NWD patients were subjected to detailed clinical evaluation. The severity of NWD was noted, and dystonia was measured by Burke-Fahn-Marsden (BFM) score. Their hematological, serum chemistry, ultrasound abdomen and cranial MRI changes were noted. Plasma GSH, TAC and MDA, serum free copper (Cu) and 24-h urinary Cu were measured at admission and at 3 and 6 months after treatment. The patients were considered worsened if there was one or more grade deterioration in severity scale, >10 % deterioration in BFM score or appearance of new neurologic signs. The median age of the patients was 11 (5-37) years, and 12 were females. Following treatment, 25 patients improved, 12 worsened, and 14 had stationary course. The worsened group at 3 months had lower GSH (1.99 ± 0.17 vs. 2.30 ± 0.30 mg/dl; P = 0.004) and TAC (1.59 ± 0.12 vs. 1.82 ± 0.17 mmol Trolox equivalent/L; P = 0.001) and higher MDA (5.24 ± 0.22 vs. 4.34 ± 0.46 nmol/ml; P < 0.001) levels compared to the improved group. These changes were associated with increased serum free Cu (41.81 ± 3.31 vs. 35.62 ± 6.40 µg/dl; P = 0.02) and 24-h urinary Cu (206.42 ± 41.61 vs. 121.99 ± 23.72 µg/24 h; P < 0.001) in the worsened compared to the improved group. All the patients having worsening were on penicillamine. Worsening following chelating treatment in NWD may be due to oxidative stress which is induced by increased serum free Cu. These results may have future therapeutic implication and needs further study.

Oxidative stress is associated with the generation of reactive oxygen species (ROS), which is supposed to be one of the mechanisms of arsenic-induced neurodegeneration. Mitochondria, being the major source of ROS generation may present an important target of arsenic-mediated neurotoxicity. Hence, we planned the study to elucidate the possible biochemical and molecular alterations induced by arsenic exposure in rat brain mitochondria. Chronic sodium arsenite treatment (25 ppm for 12 weeks) resulted in decreased activity of mitochondrial complexes I, II, and IV followed by increased ROS generation. There was decrease in mitochondrial superoxide dismutase (MnSOD) activity in arsenic-treated rat brain further showing increased superoxide radical generation in mitochondria. The decrease in MnSOD activity might be responsible for the increased protein and lipid oxidation as observed in our study. Protein and messenger RNA (mRNA) levels of MnSOD and mitochondrial uncoupling protein 2 (UCP-2) were downregulated suggesting decreased removal of ROS in rat brain. Fourier transform infrared (FTIR) spectroscopy analysis revealed significant decrease in amide A, amide I, amide II, and Olefinic = CH stretching band area suggesting molecular alteration in proteins and lipids after arsenic treatment. The results of present study indicate that arsenic-induced disturbed mitochondrial metabolism, decreased removal of ROS, decrease in protein synthesis, and altered membrane lipid polarity and fluidity may be responsible for the mitochondrial oxidative damage in rat brain that may further be implicated as contributing factor in arsenic-induced neurodegeneration.

Background: Free copper in Wilson disease (WD) is toxic and may reduce antioxidant, increase oxidative stress marker and thereby cytokine release and excitotoxic injury, but there is paucity of studies in humans. We report oxidative stress markers, cytokines and glutamate in neurologic WD and correlate these with their clinical severity, laboratory findings and extent of Magnetic resonance imaging (MRI) changes., Methods: 29 patients with neurologic WD and 9 asymptomatic WD siblings were included and their clinical, treatment history, disease severity, biochemical findings and MRI changes were noted. Glutathione (GSH), total antioxidant capacity (TAC) and malonodialdehyde (MDA) were measured by spectrophotometer, cytokines by cytokine bead array and glutamate by the fluorometer., Results: In WD patients, the glutathione (mean±SEM, 2.20±0.06 vs. 2.73±0.04mg/dl, P<0.001) and TAC (1.70±0.03 vs. 2.29±0.02 Trolox&#95;Eq&#95;mmol/l, P<0.001) were reduced, and MDA and glutamate (23.93±0.54 vs. 19.96±0.27μmol/l; P<0.001) were increased (4.7±0.11 vs. 3.03±0.52nmol/ml, P<0.001) compared to controls. The serum IL6 {median (IQRs), 9.42(10.92) vs. 5.2(5.34) pg/ml; P=0.001}, IL8 {12.37(10.92) vs. 5.63(5.52) pg/ml; P<0.001}, IL10 {8.33(8.3) vs. 2.05(1.37) pg/ml; P=0.001} and TNFα {6.14(8.95) vs. 3.61(3.58) pg/ml; P<0.001} were also increased in WD patients compared to controls. These changes were more marked in the neurologic WD compared to asymptomatic WD and in the untreated compared to treated patients. TAC correlated with duration of illness, serum free copper, 24hour urinary copper and serum ceruloplasmin, and glutamate with MDA, TNFα, ceruloplasmin and 24-hour urinary copper., Conclusions: In WD patients, antioxidants are reduced and MDA, cytokines and glutamate are increased which are more marked in symptomatic neurologic WD than asymptomatic patients., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Aluminium is light weight and toxic metal present ubiquitously on earth which has gained considerable attention due to its neurotoxic effects. The widespread use of products made from or containing aluminium is ensuring its presence in our body. There is prolonged retention of a fraction of aluminium that enters the brain, suggesting its potential for accumulation with repeated exposures. There is no known biological role for aluminium within the body but adverse physiological effects of this metal have been observed in mammals. The generation of oxidative stress may be attributed to its toxic consequences in animals and humans. The oxidative stress has been implicated in pathogenesis of various neurodegenerative conditions including Alzheimer's disease and Parkinson's disease. Though it remains unclear whether oxidative stress is a major cause or merely a consequence of cellular dysfunction associated with neurodegenerative diseases, an accumulating body of evidence implicates that impaired mitochondrial energy production and increased mitochondrial oxidative damage is associated with the pathogenesis of neurodegenerative disorders. Being involved in the production of reactive oxygen species, aluminium may impair mitochondrial bioenergetics and may lead to the generation of oxidative stress. In this review, we have discussed the oxidative stress and mitochondrial dysfunctions occurring in Al neurotoxicity. In addition, the ameliorative measures undertaken in aluminium induced oxidative stress and mitochondrial dysfunctions have also been highlighted., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Calotropis species have been used in the traditional medicinal system for the treatment of diseases of the liver and abdomen. In view of the antioxidant and anti-hyperglycemic properties of an aqueous suspension obtained from the dried latex of Calotropis procera, the present study was carried out to evaluate its efficacy in affording protection against alloxan induced changes in rat kidney. A single intraperitoneal injection of alloxan (150 mg/kg) in rats produced hyperglycemia within 3 days and altered kidney functions over a period of 90 days. Daily oral administration of the aqueous suspension (100 and 400 mg/kg) in diabetic rats produced anti-hyperglycemic effect that was comparable to that of glibenclamide (10 mg/kg). Unlike glibenclamide, the aqueous suspension did not increase the serum insulin levels in diabetic rats. However, it produced a marked reduction in the levels of urinary glucose and protein and normalized the renal tissue levels of thiobarbituric acid-reactive substances (TBARS) and glutathione (GSH) in diabetic rats and the effect was comparable to that of glibenclamide. The protection afforded by the aqueous suspension was also evident from the histological analysis of the renal tissue. Our study shows that by exhibiting antioxidant and anti-hyperglycemic property the aqueous suspension of dried latex of C. procera affords protection against the complications associated with diabetes.

The present study was undertaken to reveal the effects of chronic aluminium exposure (10 mg/kg/b.wt, intragastrically for 12 weeks) on the oxidative DNA damage and its implication on the expression of p53 and other cell-cycle regulatory proteins in male Wister rats. Chronic aluminium exposure resulted in increased formation of 8-hydoxydeoxyguanosine in the mitochondrial DNA isolated from different regions of rat brain. The agarose gel electrophoresis revealed the DNA fragmentation pattern in aluminium-treated rat brain regions. Increased expression of p53 demonstrated that aluminium induces DNA damage. Western blot and mRNA expression analysis demonstrated increased expression of cyclin D1, suggesting disruption of cell cycle. The immunohistochemical studies showed nuclear localization of p53; however, the localization of cyclin D1 was both cytoplasmic and nuclear in aluminium-treated rat brain regions. Thus, the findings of the present study reveal that aluminium-induced oxidative damage to DNA may be involved in the neurodegeneration via increase in p53 expression and activation of cell cycle.

Aluminium has been implicated in various neurodegenerative diseases but exact mechanism of action is still not known. Mitochondria being a major site of reactive oxygen species production are considered to be target of oxidative stress and it seems that the oxidative damage to mitochondrial proteins may underlie the pathogenesis of aluminium induced neurodegeneration. Thus, the present study was undertaken to reveal the effects of chronic aluminium exposure (10mg/kg b.wt, intragastrically for 12 weeks) on the oxidative damage to mitochondrial proteins in male albino Wistar rats. Chronic aluminium exposure resulted in decrease in the activity of mitochondrial superoxide dismutase (MnSOD) and aconitase in different regions of rat brain suggesting increased oxidative stress. This decrease in MnSOD activity in turn might be responsible for the increased protein oxidation as observed in our study. All these processes taken together may cause increased oxidative damage to mitochondrial proteins in general. By taking the advantage of recent immunochemical probe for oxidatively modified proteins, we identified MnSOD to be susceptible to oxidative damage in aluminium treated animals. The quantitative RT-PCR analysis for Lon protease, a protease involved in the removal of oxidatively modified proteins from mitochondria, showed decreased mRNA expression suggesting increased oxidative damage and decreased removal of mitochondrial proteins. The identification of specific proteins as targets of oxidative damage may provide new therapeutic measures to reverse the effects of aluminium induced neurodegeneration.

In view of the well-established anti-inflammatory properties of latex of Calotropis procera (DL), the present study was carried out to evaluate the protective effect of its methanol extract (MeDL) against inflammation and oxidative stress in monoarthritis induced by Freund's complete adjuvant (FCA) in rats. Intra-articular injection of FCA produced inflammation of the joint with a peak effect occurring on day 4 where a maximum increase in the levels of myeloperoxidase and inflammatory mediators like PGE2, TNF-alpha, and nitric oxide was observed. This was associated with oxidative stress with a marked reduction in the levels of glutathione, catalase, superoxide dismutase and glutathione peroxidase and an increase in the lipid peroxidation as indicated by the higher levels of thiobarbituric acid reactive substances (TBARSs). Subsequently on day 28 the histological analysis of the joint also revealed arthritic changes. Daily treatment of rats with MeDL (50 and 500 mg/kg) and standard anti-inflammatory drug rofecoxib (20 and 100 mg/kg), produced a significant attenuation in the inflammatory response and ameliorated the arthritic changes in the joint. The protection afforded by MeDL and rofecoxib was more pronounced than that of phenylbutazone and was associated with normalization of the levels of inflammatory mediators and biochemical parameters of oxidative stress. However, the overall protection afforded by rofecoxib was better than that of MeDL.

Acetamiprid (ACMP) is a neonicotinoid insecticide that poses a significant threat to the environment and mankind. Oxidative stress and mitochondrial dysfunction are considered prime contributors to ACMP-induced toxic effects. Meanwhile, berberine (BBR) a natural plant alkaloid, is a topic of interest because of its therapeutic and prophylactic actions. Therefore, this study evaluated the effects of BBR on ACMP-mediated alterations in mitochondrial functions and apoptosis in rat liver tissue. Male Wistar rats were divided into four groups: (I) control, (II) BBR-treated, (III) ACMP-exposed, and (IV) BBR+ACMP co-treated groups. The doses of BBR (150 mg/kg b.wt) and ACMP (1/10 of LD50, i.e., 21.7 mg/kg b.wt) were given intragastrically for 21 consecutive days. The results showed that the administration of ACMP diminished mitochondrial complex activity, downregulated complex I (ND1 and ND2) and complex IV (COX1 and COX4) subunit mRNA expression, depleted the antioxidant defense system, and induced apoptosis in rat liver. BBR pre-treatment significantly attenuated ACMP-induced mitochondrial dysfunction by maintaining mitochondrial complex activity and upregulating ND1, ND2, COX1, and COX4 mRNA expression. BBR reversed ACMP-mediated apoptosis by diminishing Bax and caspase-3 and increasing the Bcl-2 protein level. BBR also improved the mitochondrial antioxidant defense system by upregulating mRNA expression of PGC-1α, MnSOD, and UCP-2 in rat liver tissue. This study is the first to evaluate the protective potential of BBR against pesticide-induced mitochondrial dysfunction in liver tissue. In conclusion, BBR offers protection against ACMP-induced impairment in mitochondrial functions by maintaining the antioxidant level and modulating the apoptotic cascade. [ABSTRACT FROM AUTHOR]

Marine algae are thought to be a source of various metabolites that have a wide range of positive effects on human health. The pharmacological properties of algal metabolites, including their antioxidant, anti-inflammatory, cholesterol homeostasis, protein clearance, and anti-amyloidergic effects, lend credence to their protective efficacy against oxidative stress, neuroinflammation, mitochondrial dysfunction, and impaired proteostasis, all of which are involved in the pathophysiology of neurodegenerative disorders. There are currently no clinical trials on the effects of marine algae on neuroinflammation; however, considering the significant biological activities that have been established by in vitro and animal research, we expect that there will be clinical trials on this topic in the not-too-distant future. The most recent and important findings on the potentially neuroprotective effects of the antiinflammatory properties of marine algae were chosen for this study. Next, we conducted a literature review on the neuroprotective potential of algal compounds, along with the underlying pharmacological mechanism, and finally, we evaluated recent advances in therapeutics. [ABSTRACT FROM AUTHOR]

Acetamiprid (ACMP) is an extensively used neonicotinoid pesticide to control sucking and chewing insects and is known to cause nontarget toxicity. The present study aimed to evaluate the ameliorative potential of berberine (BBR)—a polyphenolic alkaloid‐ on ACMP‐induced oxidative stress, mitochondrial dysfunctioning, and structural changes in different rat brain regions. The male Wistar rats were divided into four groups, that is, control, BBR‐treated (150 mg/kg b.wt), ACMP‐exposed (21.7 mg/kg b.wt) and BBR + ACMP co‐treated; and were dosed intragastrically for 21 consecutive days. Results of the biochemical analysis showed that BBR significantly ameliorated ACMP‐induced oxidative stress by decreasing lipid peroxidation and protein oxidation along with a marked increase in endogenous antioxidants and lowered AChE activity in rat brain regions. Inside mitochondria, BBR significantly attenuated the toxic effects of ACMP by increasing the activity of mitochondrial complexes. Findings of polymerase chain reaction also demonstrated the modulatory effects of BBR against ACMP‐mediated downregulation of ND1, ND2, COX1, and COX4 subunits of mitochondrial complexes. The histopathological and ultrastructural examination also validated the biochemical and transcriptional alterations following toxicity of ACMP exposure and the protective potential of BBR against ACMP‐induced neurotoxicity. Thus, the present study indicates the promising ameliorative potential of BBR against ACMP‐induced neurotoxicity via its antioxidative and modulatory activities. [ABSTRACT FROM AUTHOR]

Cellular aging is the most severe risk factor for neurodegenerative disease. Simultaneously, oxidative stress (OS) is a critical factor in the aging process, resulting from an imbalance between reactive oxygen and nitrogen species and the antioxidant defense system. Emerging evidence indicates that OS is a common cause of several age-related brain pathologies, including cerebrovascular diseases. Elevated OS disrupts endothelial functional ability by diminishing the bioavailability of nitric oxide (a vascular dilator), induces atherosclerosis, and impairs vasculature, which are all common characteristics of cerebrovascular disease. In this review, we summarize evidence supporting an active role of OS in cerebrovascular disease progression, focusing primarily on stroke pathogenesis. We briefly discuss hypertension, diabetes, heart disease, and genetic factors that are often linked to OS and are considered associated factors influencing stroke pathology. Finally, we discuss the current pharmaceutics/therapeutics available for treating several cerebrovascular diseases. [ABSTRACT FROM AUTHOR]

Background:- Diabetes is a long-standing condition affecting kidneys and resulting into chronic kidney disease (CKD) as one of its major complications. In diabetic CKD there is generation of free radicals which further deteriorates kidney function. These free radicals lead to the formation of Malondialdehyde (MDA) which indicates the extent of oxidative stress (OS). Present study aims to evaluate the level of oxidative stress among diabetic CKD patients and to know its correlation with other parameters. Material and Method:- This study was comprised of 108 diabetic CKD patients from different hospitals of Lucknow in the period between November 2020 to June 2021. A control group consisting of 132 people was also taken for comparison. Study design was cross-sectional and observational. Biochemical profile including serum MDA of patient and control group was analysed using an auto analyzer. Chi-square, Pearson's correlation and t-test were applied to see association, correlation & comparison respectively between different variables. P-value was considered statistically significant if it is <0.01 for Pearson's correlation and <0.05 for other tests. Results:- Statistically significant rise in blood urea, serum creatinine, uric acid and MDA in diabetic CKD patients was observed than control group. A significant level of dyslipidemia also existed in the patients. MDA was shown to be positively and significantly correlated with serum creatinine, blood urea and serum uric acid while a negative significant correlation was there between MDA and eGFR. Conclusion:- In diabetic CKD, dyslipidemia and increased level of oxidative stress is very common. Anti-oxidant treatment and hypolipidemic therapy may be of value. Decreasing the uric acid levels may also be a new approach in the management of diabetic CKD as MDA was seen to be significantly correlated with serum uric acid. [ABSTRACT FROM AUTHOR]

The fact that oxidative stress plays an important role in the pathogenesis of various pulmonary diseases is supported by the beneficial effect of antioxidants. It is also well known that an altered oxidant-antioxidant balance after the age of 35 years increases the susceptibility to develop obstructive lung diseases later in life. Given this, the present study was designed to evaluate the effect of antioxidant supplementation on lung functions in healthy adults after the age of 35 years. Persons of age ≥35 years (n=45) were randomized into three arms (each comprising 15 participants) to receive either no intervention (NI arm), ascorbic acid 250 mg daily (AA250 arm), or ascorbic acid 500 mg daily (AA500 arm) for 6 weeks. Forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), FEV1/FVC, and peak expiratory flow (PEF) were measured at baseline and 6 weeks. Persons of age group (20–30 years) were also enrolled in the study to compare their lung functions and cardiovascular parameters at baseline with those ≥35 years of age. All the adverse events experienced by participants were recorded. Baseline pulmonary functions were found to be comparable among the three study arms and compared to ≥35 years age group, these parameters were found to be better in the younger age group (20–30 years). Most of the pulmonary functions were comparable among the three study arms at 6 weeks. A significant improvement in PEF and % predicted PEF was noted in AA250 arm when compared to baseline values (p=0.049 and 0.026, respectively) and in participants with normal pulmonary functions when compared to those with reduced functions at baseline (p=0.059 and p=0.037). Although ascorbic acid did not affect most of the pulmonary functions in healthy adults, it improved PEF and % predicted PEF at a daily dose of 250 mg. In this regard, it was found effective in individuals with normal pulmonary indices at baseline. [ABSTRACT FROM AUTHOR]

The present era's demand for continuous pesticides' use to increase the agriculture outcome, has caused numerous health effects among which mammalian infertility, owing to reproductive toxicity, is serious. Thus, the present study emphasizes upon glyphosate (GLY) induced toxicity and mitigating effects of N‐acetyl cysteine (NAC) in testicular cells of caprine by using various cytotoxic and biochemical parameters. GLY was found to induce several apoptotic attributes such as pyknotic nuclei, tubular degeneration, increased vacuolization, and so on, in testicular cells. GLY also decreased the cell viability and increased the incidence of apoptosis in testicular cells in a dose‐ and time‐dependent manner as revealed by MTT assay and Fluorescence (ethidium bromide/acridine orange) assay, respectively. It also increased the level of oxidative stress as evident with an increase in lipid peroxidation and decline in antioxidant power along with the decreased enzymatic activity of different antioxidant enzymes (SOD, CAT, and GST). However, NAC supplementation showed antagonistic results in GLY‐treated testicular tissues with maximum amelioration at the highest dose, thereby decreasing GLY‐mediated apoptosis rate and oxidative stress. Maximum amelioration was reported at 10 mM NAC concentration. Reduced GLY toxicity due to NAC will prove NAC to be an excellent approach for dealing with male reproductive toxicity at the cellular level, benefiting the mammalian reproductive status. [ABSTRACT FROM AUTHOR]

The agricultural pesticide poisoning is currently the most thrust area of human health concern. Pesticide-induced cytotoxicity and the corresponding reproductive toxicity in today's scenario is not a concealed reality that has to be considered for the continuation of respective race. Here, the transmission electron microscopy (TEM) technique was employed to investigate the adverse impact of glyphosate (GLY) and its mitigation by N-acetyl-L-cysteine (NAC) in goat testicular germ cells under in vitro conditions. The ultrastructural observations of testicular tissue from GLY-treated groups at different concentrations (0.1 and 4 mg/ml) and exposure durations (8 and 12 h) revealed that this organophosphate herbicide induced different apoptotic characteristics in testicular germ cells in a time- and dose-dependent manner. However, NAC (10 mM), being a potent antioxidant, was found to mitigate GLY-induced cytotoxicity in testicular cells as evidenced by fewer apoptotic characteristics in GLY plus NAC-treated groups, suggesting its beneficial potential in alleviating the GLY-induced gonadotoxicity in males. Abbreviations: GLY (Glyphosate), NAC (N-acetyl-L-cysteine), TEM (Transmission electron microscopic), GE (genetic engineered), Organophosphate (OPs) [ABSTRACT FROM AUTHOR]

Roxithromycin, a macrolide antibiotic, has been shown to ameliorate acetic acid induced colitis in rats by suppressing inflammation and oxidative stress. The aim of this study was to evaluate the effect of roxithromycin on small intestinal transit and cholinergic responsiveness of the colonic smooth muscles of colitic rats. Colitis was induced in rats by acetic acid and the small intestinal transit was determined by measuring the distance traversed by charcoal meal from the gastro-duodenal junction in 1 h. The test drug roxithromycin, reference drug mesalazine and anti-inflammatory drug diclofenac were administered orally before inducing colitis and their effect on intestinal transit was compared with colitic control group. The effect on cholinergic responsiveness of colonic smooth muscles was evaluated in vitro by plotting a dose-response curve using different concentrations of acetylcholine. The concentration producing 50% of maximal response (EC50) was calculated for all the treatment groups. The small intestinal transit was enhanced in colitic rats as compared to normal rats (86.00 ± 1.36 vs. 57.00 ± 1.34 cm; p<0.001). Like mesalazine, roxithromycin normalized intestinal transit while diclofenac was ineffective. The results of in vitro experiment show that colitis increased cholinergic responsiveness of the colonic smooth muscles that was not affected by roxithromycin and mesalazine while diclofenac significantly decreased it. This study shows that like mesalazine, roxithromycin affords protection in colitis mainly by normalizing propulsive movement of the small intestine than by affecting cholinergic responsiveness of the colonic smooth muscles. [ABSTRACT FROM AUTHOR]

The use of cyclosporine A (CsA) as an immunosuppressive agent is often limited owing to its hepatotoxic and nephrotoxic properties. The present study was designed to evaluate the protective effect of metformin and silymarin in a rat model of CsA induced hepatorenal toxicity. The study included seven groups of Wistar albino rats (n = 6 per group): normal control, experimental control (CsA alone, 25 mg/kg), CsA + metformin (50 and 500 mg/kg), CsA + silymarin (50 and 200 mg/kg) and CsA + vitamin E (100 mg/kg). All the drugs were given daily for a period of 21 days by oral gavage and their effect was evaluated on serum levels of organ function markers (serum glutamate pyruvate transaminase, serum glutamate oxaloacetate transaminase, bilirubin, urea/blood urea nitrogen, creatinine), markers of oxidative stress (thiobarbituric acid reactive substances, glutathione, superoxide dismutase), inflammation (nitrite, myeloperoxidase, tumour necrosis factor‐alpha, prostaglandin E2), apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labelling positivity) in addition to tissue histology, cyclooxygenase (COX)‐2 and inducible nitric oxide synthase (iNOS) immunoreactivity. Administration of metformin and silymarin along with CsA ameliorated functional damage to liver and kidneys in a dose‐dependent manner. Significant and comparable improvement in the tissue levels of oxidative stress, inflammation, apoptotic markers was also observed following treatment with both the test drugs. Normalization of histology scores, as well as COX‐2 and iNOS immunoreactivity scores, further strengthened these findings. The hepatoprotective and nephroprotective effects of metformin and silymarin were comparable and matched with that of reference drug, vitamin E. The findings of the present study suggest that both metformin and silymarin have a potential for clinical use in patients receiving long‐term CsA treatment to maintain their liver and kidney functions. [ABSTRACT FROM AUTHOR]

This review illustrates heavy metals toxicity, currently available therapies and the role and efficacy of chelation therapy for its management. Heavy metals are necessary for various biological processes, but they become harmful in excess. Specifically, they induce oxidative stress by generating free radicals and reducing antioxidant levels. Heavy metals also alter the confirmation of protein and DNA and inhibit their function. Chelation therapy is commonly used to treat metals toxicity. Chelation is a chemical process that occurs when interaction between a central metal atom/ion and ligand leads to formation of a complex ring-like structure. The ligand has a donor ion/molecule, which has a lone pair of electrons and may be monodentate to polydentate. Each metal has a different reactivity with a ligand, so a specific chelation agent is required for each metal. Combination therapy with a chelating agent and an antioxidant led to improved outcome. Heavy metal poisoning is a common health problem because of mining, smelting, industrial, agricultural and sewage waste. Heavy metals can be efficiently excreted from the body following treatment with proper chelation agents. [ABSTRACT FROM AUTHOR]

Abstract: Toxicological studies so far suggest that excessive use of malathion, an organophosphate insecticide, causes serious ill‐effects in mammalian reproductive physiology. The present study aims at assessing malathion‐induced toxicity in a dose‐ and time‐dependent manner with mitigating effects of N‐acetyl‐ l‐cysteine. The testicular germ cell viability was monitored using MTT assay, where NAC, being an antioxidant significantly reduced malathion‐induced toxicity by enhancing the frequency of cell viability. The histomorphological analysis showed that NAC successfully diminished several apoptotic features in testicular cells, induced by malathion. The differential EB/AO staining revealed a significant decline in the percentage of apoptosis after NAC supplementation. NAC also diminished the malathion‐induced DNA fragmentation along with significantly reduction in oxidative stress parameters causing decrease in lipid peroxidation and enhancement of ferric reducing antioxidant power within testicular germ cells. Thus, NAC mitigated the malathion‐induced toxicity, proving its potential in infertility treatment. [ABSTRACT FROM AUTHOR]

The present study was planned to investigate the protective effect of hydroxytyrosol (HT) against arsenic (As)-induced mitochondrial dysfunction in rat brain. Rats exposed to sodium arsenite (25 ppm for 8 weeks) showed decreased mitochondrial complexes (I, II, IV) activities, mitochondrial superoxide dismutase (MnSOD), and catalase activities in brain mitochondria. As-treated rats showed reduced mRNA expression of complex I (ND-1, ND-2), IV (COX-1, COX-4) subunits, and uncoupling protein-2 (UCP-2). In addition to this, As exposure downregulated the protein expression of MnSOD. Administration of HT with As restored the enzymatic activities of mitochondrial complexes, MnSOD and catalase, increased the mRNA levels of complexes subunits and UCP-2 as well as proteins level of MnSOD. These results suggest that HT efficiently restores mitochondrial dysfunction in As neurotoxicity and might be used as potential mitoprotective agent in future. [ABSTRACT FROM AUTHOR]

Present study was carried out to determine changes in oxidative stress biomarkers, haematological and biochemical profiles in six clinically healthy Marwari mares subjected to twenty km moderate intensity exercise on every 10th day and three Km daily, in desert sandy track in hot subtropical environment for a period of 40 days. Venous blood samples were collected for determination of selected blood parameters pre exercise and immediately post-exercise in the exercising mares and of the resting control mares. Average of last three trials of 20 Km was taken for comparison and statistical analysis. Post-exercise plasma malondialdehyde (MDA) values were significantly higher while whole blood MDA values were not significantly different from the pre exercise. In exercising mares, whole blood MDA levels were observed significantly lower than the resting control mares. Plasma MDA levels, which was observed significantly high immediately after exercise subsided after ten days and pre exercise values of plasma malondialdehyde were found not statistically different from those of the resting control mares. Thus, the findings reflected decrease in oxidative stress levels in trained Marwari horses undergoing moderate intensity exercise. Significant changes were observed in many of the biochemical and haematological parameters immediately after exercise reflected the normal physiological response of Marwari mare to moderate intensity exercise in hot environment with mild muscular damage. [ABSTRACT FROM AUTHOR]