title: Subchronic toxicity studies of the aqueous extract of Aristolochiae fructus in Sprague-Dawley rats.
abstract: The subchronic toxicity of Aristolochiae fructus containing aristolochic acids (AAs), a natural component in the Aristolochiaceae family, was investigated. The A. fructus was daily administered by gavage to male and female rats for 90 d at dose levels of 21.35, 213.5, and 2135 mg/kg (equivalent to 0.05, 0.5, and 5 mg/kg as AAs, respectively). During the test period, clinical signs, mortality, body weights, food and water consumption, hematology, serum biochemistry, organ weights, and histopathology were examined. Significant decreases in body weight gain were noted in the high-dose group receiving both the aqueous extract of A. fructus and AAs. Decreases in food consumption were noted beginning at 50 d and did not recover in the high-dose group of aqueous extract of A. fructus and AAs. Irrespective of dose, water consumption was not affected. There was no mortality or adverse clinical signs, hematology, or serum biochemistry in the treatment groups versus control. Nephrotoxicity and hyperplasia of epithelial cells in the forestomach were observed in rats receiving the highest dose of aqueous extract of A. fructus and at doses of >or= 0.5 mg/kg/day AAs. For both genders, the no-observed-adverse-effect level (NOAEL) for A. fructus based on this subchronic study in rats was considered to be 21.3 mg/kg/d.
authors.affiliation: National Institute of Toxicological Research, Korea Food and Drug Administration, Seoul.
authors.forename: Myung Sil
authors.initials: MS
authors.lastname: Hwang
authors.forename: Mi Sun
authors.initials: MS
authors.lastname: Park
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Moon
authors.forename: Ji Sun
authors.initials: JS
authors.lastname: Lee
authors.forename: Young Na
authors.initials: YN
authors.lastname: Yum
authors.forename: Eungkyung
authors.initials: E
authors.lastname: Yoon
authors.forename: Hyomin
authors.initials: H
authors.lastname: Lee
authors.forename: Ki Taek
authors.initials: KT
authors.lastname: Nam
authors.forename: Byung Mu
authors.initials: BM
authors.lastname: Lee
authors.forename: Seung Hee
authors.initials: SH
authors.lastname: Kim
authors.forename: Ki Hwa
authors.initials: KH
authors.lastname: Yang
mesh_terms: D000818:Animals; D029065:Aristolochiaceae / Q000737:chemistry*; D034341:Aristolochic Acids / Q000633:toxicity*; D005247:Feeding Behavior / Q000187:drug effects; D005260:Female; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D010936:Plant Extracts / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000187:drug effects / Q000473:pathology; D015430:Weight Gain
chemical_list: D034341:Aristolochic Acids; D010936:Plant Extracts