Protective Effect of Resveratrol on Cytotoxicity, Genotoxicity, and Oxidative Stress Caused by Cyclophosphamide and Methotrexate in Bone Marrow Stem Cell Line and Blood Lymphocytes of the Rat

Abstract

Background and Purpose: Cyclophosphamide (CP) causes damage to cancer cell DNA and oxidative stress, which occurs with decreased glutathione (GSH) and catalase and increased lipid peroxidation. However, methotrexate (MTX) may cause severe damage to the bone marrow and also cause chromosomal abnormalities in rat bone marrow after several treatments. This study aimed to investigate the protective effect of resveratrol (RES) on cytotoxicity and oxidative stress caused by CP and MTX in the stem cell (SC) line of the rat and evaluate genetic toxicity in rat blood lymphocytes. Methods: The rate of cell growth, production of reactive oxygen radicals, malondialdehyde, and GSH stores, mitochondria membrane potential in SCs, and rate of micronucleus in rat blood lymphocytes were investigated. SCs were exposed to a single dose of CP and MTX and different concentrations of RES for 48 hours. Results: CP and MTX have caused a disruption in mitochondrial function, which leads to the release of reactive oxygen radicals and increased mitochondrial membrane potential. Consequently, releasing reactive oxygen radicals caused damage to the lipid membrane and DNA while also depleting GSH reserves. However, a significant improvement was observed when SCs were exposed to RES. RES effectively scavenged reactive oxygen species and enhanced GSH reserves, improving mitochondrial function and reducing negative potential within mitochondria. Conclusions: RES showed protective effects against CP and MTX-induced cytotoxicity and genotoxicity, which may be attributed to its antioxidant activity. So, it can be considered effective against cytotoxicity and genotoxicity induced by CP and MTX in SCs and rat blood lymphocytes. © Mary Ann Liebert, Inc.