Cisplatin is a widely used cancer chemotherapeutic agent for the management of breast, metastatic ovarian, testicular,lung and neuroblastoma.A major adverse effect occurring in one of every three patients treated with cisplatin is nephrotoxicity.The development of interventions to diminish cisplatin nephrotoxicity is of direct clinical relevance.Resveratrol (3,5,4"27-trihydroxystilbene, RES), is a polyphenol, phytoalexin found ingrapes, cranberries and blueberries.RES has been recognized as a natural agent possessing anticancer properties.This study investigated the ability of RES to attenuate cisplatin renal cytotoxicity inHK-2 cells.HK-2 cells were selected for study because they are a noncancerous human kidney proximal tubular epithelial cell line.The working hypothesis was that RES will reduce cisplatin cytotoxicity in HK-2 cells by preventing or reducing the extent of oxidative stress.HK-2 cells were plated in 6 or 24 well plates and allowed to equilibrate for 48 h.Cells were pretreated for 1 h with 0-15 μM RES or vehicle prior to addition of 0-60 μM cisplatin.Cell toxicity was assessed 24 or 48 h post-cisplatin administration.Cell viability was assessed using the tetrazolium (MTT) assay.In the MTT assay, viable cells reduce MTT to formazan using a microtiter assay.Based on the MTT assay, cisplatin induced a concentration dependent loss in cell viability.RES at a concentration of 3-15 μM improved cisplatin-exposed cell viability.Further studies investigatedcisplatin mediated oxidation of amino acids on proteins as indicators of oxidative stress.Protein carbonyl formation was evaluated by Western analysis of HK-2 cells exposed to eisplatin in the presence (RES+) or absence (RES-) of RES.Cisplatin exposure induced protein carbonyl formation within 24 h in HK-2 cells compared to vehicle-treated cells.RES reduced protein carbonyl formation by cisplatin at 24 h.These findings indicated that RES was protective against cisplatin induced renal cytotoxicity in HK-2 cells and inhibited cisplatin-induced oxidative stress.RES attenuation was also associated with a decline in oxidative stress.Further studies will investigate the cellular mechanisms of protection by RES for cisplatin.