Subcellular Oxidative Stress Changes Induced by Cisplatin are reduced by Resveratrol In Vitro in Renal Tissue.

Abstract

Cisplatin, a cancer chemotherapeutic agent, can induced nephrotoxicity. Resveratrol (RES) is a natural compound found in grapes, cranberries and nuts. This study investigated whether RES reduced cisplatin renal in vitro toxicity and focused on differences between cytosolic and mitochondrial oxidative stress mediated by cisplatin. Male Fischer 344 rats (200–250 g) were anesthetized, with isoflurane and the kidneys were isolated. Renal cortical slices were prepared and pre‐incubated with 30 ul ethanol (VEH) or 30 ug/ml resveratrol (RES, final concentration) for 30 min at 37 °C and incubated 120 min with 0–150 ug/mL cisplatin. Loss of membrane integrity was evaluated as leakage of lactate dehydrogenase (LDH). Oxidative stress and nitrosative stress were assessed in mitochondria and cytosol. LDH leakage required a 120 min exposure to cisplatin. An increase in protein carbonyls as detected by Oxyblot, was increased by cisplatin and totally prevented by RES. RES also decreased protein carbonyls in tissue not exposed to cisplatin. Our findings showed that a 30 min RES pre‐incubation diminished cisplatin renal toxicity and that protein carbonyl and 3‐ nitrotyrosine and early changes in oxidative stress prior to the onset of loss of membrane integrity. (Supported by NIH Grants INBRE 3P20RR016477–09S4; 5P20RR016477 and 8P20GM103434 to the West Virginia IDeA Network for Biomedical Research Excellence).