title: Comparative nephrotoxicity of aristolochic acid and tetrandrine in vitro and in vivo.
abstract: Aristolochic acid (AA) and tetrandrine (TET) are the major bioactive components in Chinese herbs used for weight loss. The nephropathy caused by the 2 Chinese herbs has not been simultaneously investigated. The aim of this study was to examine the potential nephrotoxicity of AA and TET using Madin-Darby canine kidney (MDCK) cells and mice. The results showed that TET was more potent than AA in inhibiting MDCK cell growth via inducing apoptosis, as determined by annexin-V staining, 4', 6'-diamino-2-phenylindole (DAPI) staining, DNA fragmentation, and caspase 3 activity. Mice treated with AA (10 mg/kg) by intraperitoneal administration for 3 months showed nephrotoxicity, elevated blood urea nitrogen, and increased renal tubular injuries. In contrast, mice treated with 50 mg/kg of TET in the same time period had moderate hydropic degeneration of the distal tubules in the kidneys. These results suggest that TET is more cytotoxic than AA in MDCK cells but shows less nephrotoxic than AA in mice.
authors.affiliation: Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Sheau-Yun
authors.initials: SY
authors.lastname: Yuan
authors.forename: Chi-Rei
authors.initials: CR
authors.lastname: Yang
authors.forename: Chen-Li
authors.initials: CL
authors.lastname: Cheng
authors.forename: Shih-Lan
authors.initials: SL
authors.lastname: Hsu
authors.forename: Jiunn-Wang
authors.initials: JW
authors.lastname: Liao
authors.forename: Chi-Chen
authors.initials: CC
authors.lastname: Lin
authors.forename: Ying-Yi
authors.initials: YY
authors.lastname: Chou
authors.forename: Ya-Wen
authors.initials: YW
authors.lastname: Cheng
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D034341:Aristolochic Acids / Q000008:administration & dosage / Q000633:toxicity*; D044182:Benzylisoquinolines / Q000633:toxicity*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D053938:DNA Fragmentation; D004285:Dogs; D004365:Drugs, Chinese Herbal / Q000633:toxicity*; D007274:Injections, Intraperitoneal; D007668:Kidney / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D007677:Kidney Function Tests; D008136:Longevity / Q000187:drug effects; D051379:Mice; D008809:Mice, Inbred C3H; D009395:Nephritis, Interstitial / Q000139:chemically induced* / Q000473:pathology
chemical_list: D034341:Aristolochic Acids; D044182:Benzylisoquinolines; D004365:Drugs, Chinese Herbal; C009438:tetrandrine; C000228:aristolochic acid I