Mitochondrial oxidative damage by co-exposure to bisphenol A and acetaminophen in rat testes and its amelioration by melatonin / 대한생식의학회지

Objective@#Human exposure to multiple xenobiotics, over various developmental windows, results in adverse health effects arising from these concomitant exposures. Humans are widely exposed to bisphenol A, and acetaminophen is the most commonly used over-the-counter drug worldwide. Bisphenol A is a well-recognized male reproductive toxicant, and increasing evidence suggests that acetaminophen is also detrimental to the male reproductive system. The recent recognition of male reproductive system dysfunction in conditions of suboptimal reproductive outcomes makes it crucial to investigate the contributions of toxicant exposures to infertility and sub-fertility. We aimed to identify toxicity in the male reproductive system at the mitochondrial level in response to co-exposure to bisphenol A and acetaminophen, and we investigated whether melatonin ameliorated this toxicity. @*Methods@#Male Wistar rats were divided into six groups (n=10 each): a control group and groups that received melatonin, bisphenol A, acetaminophen, bisphenol A and acetaminophen, and bisphenol A and acetaminophen with melatonin treatment. @*Results@#Significantly higher lipid peroxidation was observed in the testicular mitochondria and sperm in the treatment groups than in the control group. Levels of glutathione and the activities of catalase, glutathione peroxidase, glutathione reductase, and manganese superoxide dismutase decreased significantly in response to the toxicant treatments. Likewise, the toxicant treatments significantly decreased the sperm count and motility, while significantly increasing sperm mortality. Melatonin mitigated the adverse effects of bisphenol A and acetaminophen. @*Conclusion@#Co-exposure to bisphenol A and acetaminophen elevated oxidative stress in the testicular mitochondria, and this effect was alleviated by melatonin.

The combination of canagliflozin and omega-3 fatty acid ameliorates insulin resistance and cardiac biomarkers via modulation of inflammatory cytokines in type 2 diabetic rats

The present study was carried out with the hypothesis that combination of canagliflozin and omega-3 fatty acid may have potential effect on insulin level, insulin resistance, cardiac biomarkers, inflammatory cytokines and histological studies in type 2 diabetes mellitus (DM). Type 2 DM was induced by injecting nicotinamide (120 mg/kg, i.p.) 15 min before STZ (60 mg/kg) injection. Canagliflozin (5 and 10 mg/kg) and omega-3 fatty acid (300 mg/kg) were given for 28 days after confirmation of diabetes. Biochemical estimations revealed elevated levels of glucose, insulin, HOMA-R and inflammatory cytokines in diabetic group. Daily dosing of alone canagliflozin and omega-3 fatty acid slightly reduced elevated levels of glucose, insulin, HOMA-R and inflammatory cytokines (IL-1β, IL-2, and TNFα), whereas canagliflozin and omega-3 fatty acid combination has reduced these biochemical parameters significantly when compared with diabetic group. Similarly in diabetic group the levels of cardiac biomarkers such as lipid profile, LDH, CKMB and troponin were significantly increased. Elevated levels of cardiac biomarkers were significantly reduced after daily dosing of alone canagliflozin and omega-3 fatty acid. Canagliflozin and omega-3 fatty acid combination has offered better improvement in cardiac biomarkers compared to alone canagliflozin and omega-3 fatty acid. Histopathological analysis also supported the above hypothesis that combination therapy (canagliflozin and omega-3 fatty acid) offered better protection against degenerative changes in β-cells of pancreas as compared to alone treatment with these drugs. Thus the present study revealed that canagliflozin and omega-3 fatty acid can be used as potential combination therapy in type 2 DM along with cardiac complication.

Comparative analysis of the protective effects of melatonin and silymarin on lipid peroxidation and dyslipidemia in STZ-induced diabetic rats

Purpose of this study was to compare the potential protective effects of Melatonin and Silymarin on blood glucose, serum lipid profile, tissue MDA and tissue glutathione in streptozotocin [STZ] induced diabetic rats. Diabetes was induced in Wistar rats by administration of a single dose of streptozotocin [60 mg/kg, i.p.] injection. STZ treatment significantly increased the levels of blood glucose, serum total cholesterol [TCh], serum triglycerides [TG] and tissue malondialdehyde [MDA], a secondary product of lipid peroxidation. On the contrary high density lipoprotein [HDL] cholesterol and glutathione [GSH] content of liver and pancreas were markedly decreased in diabetic control rats, Administration of Melatonin [16 mg/kg] and Silymarin [25 mg/ kg] caused a significant decrease in blood glucose, serum triglycerides, total cholesterol and tissue MDA with significant increase in serum HDL-cholesterol and tissue GSH content of STZ induced diabetic rats when compared with diabetic control rats. Blood glucose, serum TCh, serum TG and tissue MDA lowering effect of Melatonin was greater than that of Silymarin. Melatonin was also found to be more potent than Silymarin in increasing HDL and GSH content. Based on our findings, it is possible to postulate that Melatonin at much lower concentration is more potent than Silymarin in controlling diabetes