Modulatory effect of curcumin against genotoxicity and oxidative stress induced by cisplatin and methotrexate in male mice

Abstract

The use of dietary antioxidants to modulate the toxic side effects induced by the anticancer drugs used in chemotherapy is currently eliciting considerable interest. This study was undertaken to investigate the possible protective role of the antioxidant curcumin (CMN) against genotoxicity, cytotoxicity and oxidative stress induced by cisplatin and methotrexate. Male mice were administered CMN orally in the dosages of 60, 90, and 120 mg/kg for three consecutive days before a single intraperitoneal injection of either cisplatin (6.5 mg/kg) or methotrexate (10 mg/kg). Animals were sacrificed 24 h after treatment with the used anticancer drugs. The protective role of CMN against the genotoxic and cytotoxic effects of the tested anticancer drugs was evaluated by using micronucleus and comet assay. The oxidative stress induced by the two anticancer drugs was assessed by determining malondialdehyde and reduced glutathione levels in kidney tissues. The results indicated that CMN pretreatment at the tested doses reduced the incidence of micronuclei and DNA damage induced by cisplatin and methotrexate. Moreover, malondialdhyde level was significantly decreased while glutathione level was significantly increased in CMN pretreated groups compared with cisplatin- and methotrexate-treated groups. This protective effect of CMN could be attributed to its ability to scavenge reactive oxygen species.