title: ["Dose-time-toxicity" relationship study on hepatotoxicity caused by multiple dose of total Bupleurum saponin crude extracts to rats].
abstract: OBJECTIVE
  To study the time-toxicity and dose-toxicity relationships caused by multiple dose of total Bupleurum saponin extracts to rats.
  
  
  METHODS
  Rats were picked according to different time or dose points, and total Bupleurum saponin crude extracts were administered to rats. The death circumstance and toxicity of mice were observed, ALT and AST in serum were detected. Indice of the liver, index was calculated. And the morphological changes of liver tissue were observed under light microscope.
  
  
  RESULTS
  The "time-toxicity" relationship study showed that ALT and AST in rats' serum began to increase after 7 days' administration, and with obvious hepatotoxicity after 15 days', then there was concurrent toxicity and death. The "dose-toxicity" relationship study showed that compared with the control group, the total Bupleurum saponin crude extracts between 51. 2 and 125.0 g x kg(-1) dose could cause the obvious hepatotoxicity to rats in 15 days' administration, which was represented by that ALT and AST in serum increased significantly with the dose increased, the ratio of liver to body increased, and under light microscope, the different doses' liver tissue of mice all had edema in different degree and fatty degeneration in liver cells, and the high-dose and long time administration group appeared to be necrosis, lobular structure unclear. The above-mentioned change gradually aggravated with dose increasing, and obviously diversity compared with distilled water control group.
  
  
  CONCLUSIONS
  With administrated a multiple dose and long time to rats, the total Bupleurum saponins crude extracts could cause serious liver injury and even death, and there were certain time-toxicity and dose-toxicity relationships.
authors: Shandong Research Academy of Traditional Chinese Medicine, Jinan 250014, China.
authors: Wei
authors: W
authors: Huang
authors: Rong
authors: R
authors: Sun
authors: Zuoping
authors: Z
authors: Zhang
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D029972:Bupleurum / Q000737:chemistry*; D045424:Complex Mixtures / Q000008:administration & dosage* / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012503:Saponins / Q000737:chemistry*; D013997:Time Factors; D018675:Toxicity Tests / Q000379:methods*
chemical_list: D045424:Complex Mixtures; D012503:Saponins; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase