The protective effect of melatonin on diazepam-induced genotoxicity in peripheral blood lymphocytes using micronucleus assay

Abstract

Background: Diazepam belongs to the benzodiazepine family of drugs and is mainly used for anxiety, muscle spasms, seizures, and insomnia. Long-term diazepam administration can cause genotoxicity, and oxidative stress is a likely molecular mechanism involved. Objectives: In this study, the benefits of melatonin against diazepam-induced oxidative damage and genotoxicity were investigated. Materials and Methods: Cultured peripheral lymphocytes were allocated to five groups: control, diazepam (100 μg/mL), melatonin (50 and 100 μM) with diazepam and cisplatin (0.05 μg/mL). After harvesting and preparing slides, the incidence of micronuclei (MN) was observed as a marker of genotoxicity. Then, in order to measure oxidative stress parameters, contents of glutathione (GSH) and lipid peroxidation (LPO) were determined. Results: Results documented increased MN and LPO and decrease in GSH levels in diazepam-administered lymphocytes versus those of the control group. When melatonin was given to diazepam-administered lymphocytes, they almost attenuated the increase of MN and LPO and restored the levels of GSH. Conclusion: Results showed that diazepam seems to induce genotoxicity in cultured human lymphocytes and oxidative stress plays an important role in it. Furthermore, it is concluded that melatonin efficiently protects against genotoxicity through its anti-oxidative effects.