Nephrotoxicity of Aristolochia manshuriensis and aristolochic acids in mice.
- Author:
Xiao-shuang DING
1
;
Ai-hua LIANG
;
Jin-hua WANG
;
Yong-qing XIAO
;
Zi-lun WU
;
Chun-ying LI
;
Li LI
;
Rong HE
;
Lian-qiang HUI
;
Bao-yan LIU
Author Information
- Publication Type:Journal Article
- MeSH: Alanine Transaminase; blood; Animals; Aristolochia; chemistry; Aristolochic Acids; administration & dosage; isolation & purification; toxicity; Aspartate Aminotransferases; blood; Blood Urea Nitrogen; Creatinine; blood; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; administration & dosage; isolation & purification; toxicity; Female; Kidney; pathology; Lethal Dose 50; Liver; pathology; Male; Mice; Mice, Inbred ICR; Random Allocation
- From: China Journal of Chinese Materia Medica 2005;30(13):1019-1022
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVEThe 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.
METHODA 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.
RESULTLD50 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.
CONCLUSIONGMT 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.