title: [Nephrotoxicity of Aristolochia manshuriensis and aristolochic acids in mice].
abstract: OBJECTIVE
  The acute toxic effects of Aristolochia manshuriensis (GMT) and the total aristolochic acids (TA) were compared in mice with aristolochic acid A (AA) as the dose standard. The dose relationship of the renal toxicity induced by Aristolochia manshuriensis was determined.
  
  
  METHODS
  A single dose of GMT extract or TA was given intragastrically to mice at different doses. LD50 values, the blood levels of BUN, Cr and ALT were measured. A histomorphological study was also performed in livers and kidneys of mice.
  
  
  RESULTS
  LD50 value of GMT extract was 4.4 g x kg(-1) which was equivalent to 40 mg x kg(-1) as calculated by the content of AA in GMT extract, and this value was comparable with LD50 obtained from TA given intragastrically in mice (equivalent to 33 mg x kg(-1) of AA for male and 37 mg x kg(-1) for female). GMT extract caused a significant increase in blood BUN and Cr and an obvious morphological change in kidney in a dose-dependent manner at doses of AA 4.5 mg x kg(-1) and above. Liver damage, characterized by both an increase in blood level of AST and histomorphological change, was observed at doses of AA 25 mg x kg(-1) and above. All changes were in proportion to the doses of AA.
  
  
  CONCLUSIONS
  GMT causes both renal and liver toxicity. The dose leading to nephrotoxicity is much lower than that inducing hepatatoxicity. Aristolochic acids existed in GMT are the main toxic components to cause renal toxicity which is a crucial cause to result in death. The lethality and nephrotoxicity of GMT is in proportion to the doses of AA.
authors.affiliation: The Institute of Chinese Materia Medica, Chinese Academy of Traditional Chinese Medicine, Beijing 100700, China.
authors.forename: Xiao-shuang
authors.initials: XS
authors.lastname: Ding
authors.forename: Ai-hua
authors.initials: AH
authors.lastname: Liang
authors.forename: Jin-hua
authors.initials: JH
authors.lastname: Wang
authors.forename: Yong-qing
authors.initials: YQ
authors.lastname: Xiao
authors.forename: Zi-lun
authors.initials: ZL
authors.lastname: Wu
authors.forename: Chun-ying
authors.initials: CY
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Rong
authors.initials: R
authors.lastname: He
authors.forename: Lian-qiang
authors.initials: LQ
authors.lastname: Hui
authors.forename: Bao-yan
authors.initials: BY
authors.lastname: Liu
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D030022:Aristolochia / Q000737:chemistry; D034341:Aristolochic Acids / Q000008:administration & dosage / Q000302:isolation & purification / Q000633:toxicity*; D001219:Aspartate Aminotransferases / Q000097:blood; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000302:isolation & purification / Q000633:toxicity*; D005260:Female; D007668:Kidney / Q000473:pathology*; D007928:Lethal Dose 50; D008099:Liver / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011897:Random Allocation
chemical_list: D034341:Aristolochic Acids; D004365:Drugs, Chinese Herbal; D003404:Creatinine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase