title: [Toxic effects of aqueous extract of crotalariae assamicae semen in rats and possible mechanism in association with liver damage].
abstract: OBJECTIVE
  To study the toxic effects of aqueous extract of Crotalariae Assamicae Semen (CAS), one of the pyrrolizidine alkaloid-containing Chinese herbal medicines, in rats and the possible mechanism in association with liver damage.
  
  
  METHODS
  The aqueous extract of CAS (CASE) was prepared by the conventional water extracting-alcohol precipitating method. The LD50 value of CASE in rats was determined by Kärber method. Rats were randomly divided into four groups in which three groups were orally administered with different doses of the CASE and one group with distilled water as control. Toxic effects were assessed by morphological, biochemical and histopathological changes. Moreover, in vitro metabolism using rat liver microsomes was also conducted and applied for the exploration of the underlying mechanism of liver damage.
  
  
  RESULTS
  The LD50 value of CASE in Wistar rats was (2.36 +/- 0.26) g x kg(-1). The toxic effects were found in all groups of rats dosed with CASE, in which serum levels of ALT and AST were significantly elevated, and the obvious and dose-dependent damages in liver and lung were observed by histopathological examination. Moreover, the liver tissue-bound pyrroles were detected and generated in a dose-dependent manner, and the pyrrole metabolites observed in the in vitro microsomal metabolism. All the evidences suggested a strong correlation between metabolism and toxicity of CASE in rats.
  
  
  CONCLUSIONS
  CASE could induce the acute toxicity in rats, of which liver and lung were the major targets. Toxic effects were strongly correlated with pyrrolizidine alkaloids in CAS. The possible mechanism for its liver toxicity may be related to the formation of pyrrole metabolites as well as the corresponding tissue-binding products.
authors.affiliation: Wuhan Institute for Food and Drug Control, Wuhan 430012, China. xiaomaocheng2@163.com
authors.forename: Min
authors.initials: M
authors.lastname: Cheng
authors.forename: Jun
authors.initials: J
authors.lastname: Tang
authors.forename: Li-Qun
authors.initials: LQ
authors.lastname: Jiang
authors.forename: Zi-Ming
authors.initials: ZM
authors.lastname: Jia
authors.forename: Masao
authors.initials: M
authors.lastname: Hattori
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D029864:Crotalaria / Q000737:chemistry*; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000633:toxicity*; D007928:Lethal Dose 50; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000293:injuries; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D011763:Pyrrolizidine Alkaloids / Q000008:administration & dosage / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004365:Drugs, Chinese Herbal; D011763:Pyrrolizidine Alkaloids; D000410:Alanine Transaminase