title: Dual effects of quercetin in doxorubicin-induced nephrotoxicity in rats and its modulation of the cytotoxic activity of doxorubicin on human carcinoma cells.
abstract: 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.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University, El-Minia, Egypt.
authors.forename: Gehan H
authors.initials: GH
authors.lastname: Heeba
authors.affiliation: Department of Agricultural Chemistry, Faculty of Agriculture, Minia University, El-Minia, Egypt.
authors.forename: Magda E
authors.initials: ME
authors.lastname: Mahmoud
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology*; D001806:Blood Urea Nitrogen; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D003404:Creatinine / Q000097:blood; D004317:Doxorubicin / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D061986:MCF-7 Cells; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011794:Quercetin / Q000494:pharmacology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D053583:Interleukin-1beta; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D008315:Malondialdehyde; D004317:Doxorubicin; D011794:Quercetin; D003404:Creatinine; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D053148:Caspase 3; D005978:Glutathione
keywords: apoptosis; cytotoxicity; doxorubicin; nephrotoxicity; oxidative stress; quercetin