Cisplatin Mediated Alterations in Oxidative Stress Enzymes are Modulated by Resveratrol

Abstract

Resveratrol (RES) is a phytochemical possessing anticancer and antioxidant properties. This study examined whether RES would reduce cisplatin renal toxicity and associated oxidative stress. Male Fischer 344 rats (200–250 g) were anesthetized, renal cortical slices prepared and pre-incubated with 30 ul ethanol (VEH) or 30 ug/ml resveratrol (RES, final concentration) for 30 min at 37°C under an oxygen atmosphere. Tissue was then incubated for 120 min with 0, 75, or 150 ug/mL cisplatin. Loss of membrane integrity was evaluated as leakage of lactate dehydrogenase (LDH). 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. GSH peroxidase activity was diminished by cisplatin when compared to vehicle control beginning at 60 min. Total SOD activity was also diminished by cisplatin beginning at 60 min. RES reduced oxidative stress by maintaining GSH peroxidase enzyme activity. Total SOD enzyme activity was preserved by RES co-incubation with cisplatin. In summary. A 30 min RES pre-incubation diminished cisplatin renal toxicity and early changes in oxidative stress prior to the onset of LDH leakage. (Supported by NIH Grant INBRE 3P20RR016477-09S4).