title: Vitamin C attenuates the toxic effect of aristolochic acid on renal tubular cells via decreasing oxidative stress‑mediated cell death pathways.
abstract: Aristolochic acid (AA) is a component of Chinese medicinal herbs, including asarum and aristolochia and has been used in Traditional Chinese Medicine for a long time. Recent studies found that AA has a cytotoxic effect resulting in nephropathy. These studies indicated that AA‑induced cytotoxicity is associated with increases in oxidative stress and caspase‑3 activation. The present study further demonstrated that AA mainly elevates the H2O2 ratio, leading to increases in oxidative stress. Furthermore, the results indicated that AA induces cell death can via caspase‑dependent and ‑independent pathways. It is desirable to identify means of inhibiting AA‑induced renal damage; therefore, the present study applied an anti‑oxidative nutrient, vitamin C, to test whether it can be employed to reduce AA‑induced cell cytotoxicity. The results showed that vitamin C decreased AA‑induced H2O2 levels, caspase‑3 activity and cytotoxicity in renal tubular cells. In conclusion, the present study was the first to demonstrate that AA‑induced increases of the H2O2 ratio resulted in renal tubular cell death via caspase‑dependent and ‑independent pathways, and that vitamin C can decrease AA‑induced increases in H2O2 levels and caspase‑3 activity to attenuate AA‑induced cell cytotoxicity.
authors.affiliation: The Ph.D. Program for Cancer Biology and Drug Discovery, China Medical University and Academia Sinica, Taichung 404, Taiwan, R.O.C.
authors.forename: Tsai-Kun
authors.initials: TK
authors.lastname: Wu
authors.affiliation: Deparment of Nutrition, Hungkuang University, Taichung 433, Taiwan, R.O.C.
authors.forename: Chyou-Wei
authors.initials: CW
authors.lastname: Wei
authors.affiliation: Deparment of Nutrition, Hungkuang University, Taichung 433, Taiwan, R.O.C.
authors.forename: Ying-Ru
authors.initials: YR
authors.lastname: Pan
authors.affiliation: Deparment of Biotechnology, Hungkuang University, Taichung 433, Taiwan, R.O.C.
authors.forename: Shur-Hueih
authors.initials: SH
authors.lastname: Cherng
authors.affiliation: Graduate Institute of Cancer Biology and Center for Molecular Medicine, China Medical University, Taichung 404, Taiwan, R.O.C.
authors.forename: Wei-Jung
authors.initials: WJ
authors.lastname: Chang
authors.affiliation: Deparment of Nutrition, Hungkuang University, Taichung 433, Taiwan, R.O.C.
authors.forename: Hsueh-Fang
authors.initials: HF
authors.lastname: Wang
authors.affiliation: The Ph.D. Program for Cancer Biology and Drug Discovery, China Medical University and Academia Sinica, Taichung 404, Taiwan, R.O.C.
authors.forename: Yung-Luen
authors.initials: YL
authors.lastname: Yu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D030022:Aristolochia / Q000737:chemistry; D034341:Aristolochic Acids / Q000633:toxicity*; D030023:Asarum / Q000737:chemistry; D001205:Ascorbic Acid / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000633:toxicity; D006861:Hydrogen Peroxide / Q000378:metabolism; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology; D007684:Kidney Tubules / Q000166:cytology* / Q000187:drug effects*; D018384:Oxidative Stress; D051381:Rats
chemical_list: D034341:Aristolochic Acids; D004365:Drugs, Chinese Herbal; C000228:aristolochic acid I; D006861:Hydrogen Peroxide; C505410:Casp3 protein, rat; D053148:Caspase 3; D001205:Ascorbic Acid