Modulatory Effects of Dexrazoxane Against Genotoxicity and Lipid Peroxidation Induced by Idarubicin in Hepg2 Cells Publisher



Zarifi F¹ ; Etebari M¹ ; Jafariandehkordi A¹ Show Affiliations
Source: International Journal of Cancer Management Published:2018

Abstract

Background: Idarubicin is an anthracycline antibiotic drug widely used in chemotherapy. Dexrazoxane is an iron chelator used clinically against anthracyclines-induced cardiotoxicity. The present study was designed to determine the possible genoprotection of dexrazoxane on idarubicin-induced DNA damage and oxidative stress. Methods: In this study, the induction of DNA damage by idarubicin was examined on HepG2 cells, using comet assay. Cells were exposed to different concentrations of idarubicin in order to find the minimum and suitable genotoxic concentration. To survey the genoprotective effects of dexrazoxane, cells were subjected to several safe concentrations of dexrazoxane (10, 50, 100, and 200 µM) for 24 hours followed by 1 hour exposure to established genotoxic concentration of idarubicin (0.05 µM). Lipid peroxidation was assessed as a biomarker to show the index of oxidative stress and a possible mechanism underlying this amelioration. Results: Dexrazoxane pre-treatment significantly reduced different parameters of DNA migration such as tail length, % DNA in tail, andtailmoment. Moreover, the treatment of dexrazoxane (200µM)decreased the severity of idarubicin-induced lipid peroxidation. Conclusions: Dexrazoxane in addition to cardioprotection against idarubicin-induced cardiotoxicity has the potential to attenuate its DNA damage and lipid peroxidation in normal cells of patients with cancer treated with idarubicin. © 2018, Cancer Research Center (CRC), Shahid Beheshti University of Medical Sciences.