Metformin attenuates cisplatin-induced genotoxicity and apoptosis in rat bone marrow cells

Abstract

Metformin is widely used as an oral hypoglycemic drug in the management of type 2 diabetes mellitus. This study evaluated the possible protective effects of metformin against cisplatin-induced genotoxicity and apoptosis in rat bone marrow cells. Two different doses of metformin (50 and 100 mg/kg b.w.) were administered orally to experimental animals for seven consecutive days. On the seventh day, the rats were exposed to cisplatin (5 mg/kg, i.p.) 1 h after the last oral metformin administration. Rats in the control group were treated orally with 10 ml/kg PBS for 7 consecutive days and a single intraperitoneal injection of saline (0.9%) on the 7th day. The antagonistic effects of metformin against cisplatin were evaluated using micronucleus assay, reactive oxygen species (ROS) level analysis, hematological analysis, and flow cytometry. Treatment with 50 and 100 mg/kg metformin before cisplatin injection produced a significant reduction in the frequencies of micronucleated polychromatic erythrocytes (MnPCEs) and micronucleated normochromatic erythrocytes (MnNCEs) 24 h after cisplatin treatment with a corresponding increase in the PCE/(PCE + NCE) ratio. Moreover, metformin markedly elevated the levels of both red and white blood cells in peripheral blood and decreased the percentage of apoptotic cells and the ROS level in bone marrow cells of rats treated with cisplatin. The data suggest that metformin has potential chemoprotective properties in rat bone marrow after cisplatin treatment, which support its candidature as a potential chemoprotective agent for cancer patients undergoing chemotherapy.