Resveratrol Reduces Cisplatin Mediated Oxidative Modifications of Proteins and Oxidative Stress Enzyme Activity in Renal Rat Tissue

Abstract

Nephrotoxicity is an adverse effect associated with the cancer chemotherapeutic agent cisplatin. (RES) is a phytochemical found in grapes which possesses anticancer and antioxidant properties. This study investigated RES attenuation of cisplatin renal cytotoxicity and reduction in oxidative stress mediated by cisplatin. Kidneys were isolated from male Fischer 344 rats and renal slices were pre‐incubated with 30 ul ethanol (VEH) or 30 ug/ml resveratrol (RES, final concentration) for 30 min. Tissue were immediately incubated for a maximum of 120 min with 0–75 ug/mL cisplatin. Loss of membrane integrity was measured as lactate dehydrogenase (LDH) leakage. Cisplatin associated oxidative stress was evaluated by measuring total, Cu/Zn and Mn Superoxide dismutase (SOD), glutathione peroxidase and catalase enzyme activity in renal cortical slices. LDH leakage required a 120 min exposure to cisplatin. Cisplatin alter GSH peroxidase and SOD within 60 min when compared to VEH group. RES reduced oxidative stress by maintaining GSH peroxidase and SOD enzyme activity. An increase in protein carbonyls as detected by Oxyblot, was increased by cisplatin and totally prevented by RES. Our findings showed RES diminished cisplatin renal toxicity and early changes in oxidative stress. (Supported by NIH Grants INBRE 3P20RR016477‐09S4 and 5P20RR016477 to the West Virginia IDeA Network for Biomedical Research Excellence).