Melatonin's protective effect against placental transfer of Methadone in mice: An experimental study

Background: 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 a hormone with antioxidant activity. Objective: This study aimed to evaluate the protective effects of melatonin on oxidative stress induced by the transfer of transplacental methadone in mice. Materials and Methods: In this experimental study, ۳۶ female mice (۲ months old, ۲۰ ± ۲ gr) were divided into ۶ groups (n = ۶/each) of control, methadone (۰.۳ mg/kg intraperitoneal, single dose) and melatonin (۲, ۴, and ۶ mg/kg/day gavage) were administered ۳۰ min before methadone, and one group received melatonin alone (۰.۶ mg/kg with single injection). Administration for ۱۰ consecutive days of the pregnancy period was done. After baby mice were born, all neonatal mice were killed by beheading or sacrificing after anesthesia. The liver tissues were extracted. The samples were then sent for studying oxidative stress markers such as lipid peroxidation, glutathione, and protein carbonyl contents. Also, we have used the immunohistochemistry method for apoptotic markers such as: BAX, Bcl۲, and Caspase۳ for assaying apoptosis. Results: This study has shown that methadone caused a significant decrease in glutathione concentration (p = ۰.۰۳۵). Also, we observed a significant increase in lipid peroxidation and protein carbonyl contents (p = ۰.۰۱۵, ۰.۰۲۵ respectively). However, melatonin treatment significantly inhibited oxidative stress markers (p = ۰.۰۲۵). Also, apoptosis assay has shown that melatonin could decrease BAX and Caspase ۹ as apoptotic and increase Bcl۲ as an antiapoptotic proteins (p = ۰.۰۱۵). Conclusion: Our findings have shown that melatonin has a protective effect against oxidative stress and apoptosis induced by the placental transfer of methadone via its antioxidant effects.

کلیدواژه ها:

Oxidative stress ، Methadone ، Melatonin ، Pregnancy. ، استرس اکسیداتیو ، متادون ، ملاتونین ، بارداری.