Published date: Sep 03 2024

Journal Title: International Journal of Reproductive BioMedicine

Issue title: International Journal of Reproductive BioMedicine (IJRM): Volume 22, Issue No. 7

Pages: 515–526

DOI: 10.18502/ijrm.v22i7.16957

Maryam Akbarzadeh

Ramin Ataee

Farkhondeh Nemati - f.namati@qaemiau.ac.ir

Abbas Ali Dehpouri

Fatemeh Shaki

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, 36 female mice (2 months old, 20 ± 2 gr) were divided into 6 groups (n = 6/each) of control, methadone (0.3 mg/kg intraperitoneal, single dose) and melatonin (2, 4, and 6 mg/kg/day gavage) were administered 30 min before methadone, and one group received melatonin alone (0.6 mg/kg with single injection). Administration for 10 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, Bcl2, and Caspase3 for assaying apoptosis.

Results: This study has shown that methadone caused a significant decrease in glutathione concentration (p = 0.035). Also, we observed a significant increase in lipid peroxidation and protein carbonyl contents (p = 0.015, 0.025 respectively). However, melatonin treatment significantly inhibited oxidative stress markers (p = 0.025). Also, apoptosis assay has shown that melatonin could decrease BAX and Caspase 9 as apoptotic and increase Bcl2 as an antiapoptotic proteins (p = 0.015).

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.

Key words: Oxidative stress, Methadone, Melatonin, Pregnancy

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