title: Evaluation of the liver protection and toxicity of Da-Huang-Zhe-Chong pill in rats.
abstract: BACKGROUND
  Da-Huang-Zhe-Chong pill (DHZCP), a classical traditional Chinese formula, consists of 12 crude drugs which have been widely used with significant therapeutic effects. Some drugs in this formula have toxicities that might result in some adverse effects of DHZCP.
  
  
  OBJECTIVE
  The liver protection and toxicity of DHZCP were first evaluated against chronic carbon tetrachloride (CCl(4))-induced liver injury in rats.
  
  
  METHODS
  The rats were treated by intraperitoneal injection of 10% CCl(4) for 12 weeks. At the end of week 4, DHZCP at doses of 44 g/kg (high-dose group) and 22 g/kg (low-dose group) was intragastrically administered to CCl(4)-treated rats, once a day for four weeks. At the end of weeks 8 and 12, the general status of the rats, histopathology of liver, serum alanine aminotransaminase (ALT), aspartate aminotransaminase (AST), alkaline phosphatase (ALP) and total bilirubin (TBIL) levels were observed or determined and recorded. By correspondence analysis (CA) on biochemical markers and liver histopathological score (HS), the "dose-time-response" relationship of DHZCP on the hepatic injury rats was evaluated.
  
  
  RESULTS
  The results showed that DHZCP exhibited a significant protective effect on liver injury by reversing the biochemical parameters and histopathological changes. However, this hepatoprotective effect may be weakened, or even be transferred to toxicity with the increase of the administration dose (44 g·kg(-1)·d(-1)) and time (more than 2 months) of this formula. These results were consistent with the histopathological observation and the serum levels.
  
  
  CONCLUSIONS
  Administration of proper dose and time of DHZCP could well play its hepatoprotective effect and even treat hepatitis, but the safety on liver should be considered when large-dose (44 g·kg(-1)·d(-1)) DHZCP is used for long time (more than 2 months). We suggest that the administration dose and time of DHZCP in clinical use should not be increased and prolonged, and simultaneously liver function should be regularly monitored.
authors: China Military Institute of Chinese Materia Medica, 302 Military Hospital of China, Beijing, PR China.
authors: Xiao-yan
authors: XY
authors: Xing
authors: Yan-ling
authors: YL
authors: Zhao
authors: Lei
authors: L
authors: Jia
authors: Wei-jun
authors: WJ
authors: Kong
authors: Yan-wei
authors: YW
authors: Zhong
authors: Jia-bo
authors: JB
authors: Wang
authors: Ping
authors: P
authors: Zhang
authors: Hui-ling
authors: HL
authors: Ren
authors: Xiao-he
authors: XH
authors: Xiao
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D005260:Female; D007274:Injections, Intraperitoneal; D008107:Liver Diseases / Q000503:physiopathology / Q000517:prevention & control*; D008111:Liver Function Tests; D008297:Male; D020011:Protective Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: C521634:Dahuang Zhechong pill; D004365:Drugs, Chinese Herbal; D020011:Protective Agents; D002251:Carbon Tetrachloride