Quercetin (QUR) has been shown to induce anti-, as well as, pro-oxidant effects depending on the dose and on the redox state of the cell. This study investigated the effects of different doses of QUR on doxorubicin (DOX)-induced nephrotoxicity in rats with emphasis on the suggested mechanisms and its modulation of the cytotoxic activity of DOX on different human carcinoma cell lines. Three doses of QUR (10, 50, and 100 mg kg(-1)) were administered orally to adult male albino rats for 14 days, in the presence or absence of nephrotoxicity induced by a single intraperitoneal injection of DOX (15 mg kg(-1)) at day 7 of the experiment. Moreover, the effect of QUR in the presence of DOX on the cell viability of four different human cancer cell lines; PC3, HELA, MCF7, and HEPG2 was studied. Results showed that the lowest dose of QUR was more effective in preserving renal function (kidney index, blood urea nitrogen, serum creatinine, renal malondialdehyde, nitric oxide, reduced glutathione, catalase activity, renal expressions of TNF-α, IL-1B, iNOS, and caspase-3, and renal histopathology) than higher doses. Alternatively, the pro-oxidant and pro-inflammatory mechanisms have been reflected at highest QUR dose. In conclusion, QUR protected against DOX-induced nephrotoxicity with a provision to dosage adjustment. Furthermore, QUR did not interfere but rather enhanced the cytotoxic effects of DOX on different human cancer cell lines.
Keywords: apoptosis; cytotoxicity; doxorubicin; nephrotoxicity; oxidative stress; quercetin.
© 2014 Wiley Periodicals, Inc.