Evaluation of Melatonin protective effect on reducing oxidative stress and apoptosis by placental transfer of Methadone in Mice

Abstract

Abstract Methadone is a substance widely used in the substitution treatment of opiate addiction in pregnancy. The placental transfer of methadone influences oxidative stress processes. Melatonin is the hormone with antioxidant activity. This study aimed to evaluate the protective effects of melatonin on oxidative stress induced by transfer of transplacental methadone in mice After breading and mating periods,the female mice (25-30 gm, 2 months old) were divided into 6 groups (6 mice per group) of control, Methadone (0.3 mg/kg intraperitoneal, single dose) and melatonin (0.2, 0.4, and 0.6 mg/kg/day gavage) administered 30 minutes before methadone and one group received melatonin alone(0.6 mg/kg) . All groups were received as a single injection. Administration for 10 consecutive days of pregnancy period were done. After Baby mice were born, all neonatal mice were killed with beheading. Then, the liver tissues were brought out. Then samples were gone for studying of oxidative stress markers as lipid peroxidation (LPO), glutathione (GSH), and protein carbonyl (PrC) contents.Also for assaying apoptosis we have used immunohistochemistry method for BAX, Bcl2 and Caspase3. This study has shown that methadone caused a significant decrease in GSH concentration<0.05. Also were observed a significant increase in lipid peroxidation (LPO) and protein carbonyl contents<0.05. However, melatonin treatment significantly inhibited oxidative stress markers<0.05 .Also apoptosis assay has shown that melatonin could decrease BAX and Caspase 3 as apoptotic proteins and increased Bcl2 as anti-apoptotic protein (P<0.05).Our findings have shown that melatonin has a protective effect against oxidative stress and apoptosis induced by placental transfer of methadone via its antioxidant effects.