"Pharmacological study on the potential effect of piceatannol on cisplatin- induced nephrotoxicity in rats"

Abstract

Cisplatin induced nephrotoxicity is a major side effect limiting its chemotherapeutic use. We investigated whether piceatannol (PIC)can protect against cisplatin-induced nephrotoxicity in rats and the potential underlying mechanisms. A single dose of cisplatin (7mg/kgi.p.) was used to induce nephrotoxicity and PIC was given in different daily doses (5, 10 and 20 mg/kg i.p.), for seven days starting two days before cisplatin injection. Cisplatin significantly increased blood urea nitrogen and serum creatinine levels and induced tubular degeneration, hemorrhage and cast formation. PIC at dose 10 mg/kg was effective in preventing these alterations. In subsequent mechanistic study, PIC (10 mg/kg i.p.) reversed cisplatin-induced kidney injury molecule 1 and neutrophil gelatinase associated lipocalin and ameliorated cisplatin-induced oxidative stress, inflammation and apoptosis. PIC inhibited cisplatin-induced lipid peroxidation and glutathione depletion. Additionally, PIC reversed cisplatin-induced reduction in the gene expression of nuclear factor E2-related factor 2 and the relative mRNA level of antioxidant related genes; hemeoxygenase-1, cysteine ligase catalytic and modifier subunits, as well as superoxide dismutase and glutathione-S-transferase activities. Furthermore, cisplatinproinflammatory response was reduced by PIC treatment as evidenced