[Nephrotoxicity of Aristolochia manshuriensis and aristolochic acids in mice].
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.
Ding
Xiao-shuang
XS
The Institute of Chinese Materia Medica, Chinese Academy of Traditional Chinese Medicine, Beijing 100700, China.
Liang
Ai-hua
AH
Wang
Jin-hua
JH
Xiao
Yong-qing
YQ
Wu
Zi-lun
ZL
Li
Chun-ying
CY
Li
Li
L
He
Rong
R
Hui
Lian-qiang
LQ
Liu
Bao-yan
BY
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
D034341:Aristolochic Acids; D004365:Drugs, Chinese Herbal; D003404:Creatinine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase