Antioxidant and Genoprotective Effects of Amifostine against Irinotecan Toxicity in Human Hepatoma Cells

Abstract

Irinotecan (CPT-11) is a topoisomerase inhibitor anticancer drug effective against many human malignancies. Several mechanisms have been proposed for the antitumor effects of irinotecan, such as DNA synthesis inhibition, DNA crosslinking, inhibition of topoisomerase I, free radical generation and lipid peroxidation. Amifostine, is a cytoprotective adjuvant used in cancer chemotherapy, involving DNA-binding chemotherapeutic agents. The aim of this study was to explore whether amifostine protects against irinotecan-induced genotoxicity in HepG2 cells. For this purpose, we measured the DNA damage level with comet assay in HepG2 cells treated with irinotecan and amifostine in different condition. We also measured the intracellular ROS generation and GSH levels in cells treated with irinotecan and amifostine in pre-treatment condition. Our results showed that irinotecan induced a noticeable genotoxic effect in HepG2 cells. Amifostine reduced the effects of irinotecan significantly (p<0.0001) by reduction of the level of DNA damage via blocking ROS generation, and enhancement of intracellular glutathione levels.