title: Investigation of the "dose-time-response" relationships of rhubarb on carbon tetrachloride-induced liver injury in rats.
abstract: OBJECTIVE
  The present study investigated the liver protection and toxicity of rhubarb against carbon tetrachloride (CCl4)-induced chronic liver injury in rats.
  
  
  METHODS
  The rats were treated by intraperitoneal injection of 10% CCl4 for 12 weeks. At the end of week 4, rhubarb at doses of 40 g kg(-1) (high-dose group), 20 g kg(-1) (medium-dose group) and 10 g kg(-1) (low-dose group) was intragastrically administered to CCl4-treated rats once a day for three weeks. At the end of week 16, all rats were maintained for 1 month without any administration. At the end of weeks 8, 12, 16 and 20, the general status of rats, histopathology of liver, serum alanine aminotransaminase (ALT), aspartate aminotransaminase (AST), total bilirubin (TBIL) and hyaluronic acid (HA) levels were observed, respectively. Combined with clustering analysis and correspondence analysis, the "dose-time-response" relationships of rhubarb on the liver injury rats were synthetically investigated.
  
  
  RESULTS
  High dose (40 g kg(-1)) of rhubarb exhibited a significant protective effect on injured liver by reversing the biochemical parameters and histopathological changes. But, this hepatoprotective effect will be weakened, even be transferred to toxicity with increasing the administration dose and time of rhubarb. These results were consistent with the histopathological observation and the determination of serum levels.
  
  
  CONCLUSIONS
  The safety should be considered simultaneously in the long-term and high dose use of rhubarb, the liver function and change should be regularly detected. This study provided some useful references for the clinical rational use of rhubarb and other herbal medicinal products.
authors.affiliation: China Military Institute of Chinese Materia Medica, 302 Military Hospital of China, Beijing 100039, PR China.
authors.forename: Xiao-yan
authors.initials: XY
authors.lastname: Xing
authors.forename: Yan-ling
authors.initials: YL
authors.lastname: Zhao
authors.forename: Wei-jun
authors.initials: WJ
authors.lastname: Kong
authors.forename: Jia-bo
authors.initials: JB
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Jia
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.forename: Dan
authors.initials: D
authors.lastname: Yan
authors.forename: Yan-wei
authors.initials: YW
authors.lastname: Zhong
authors.forename: Rui-sheng
authors.initials: RS
authors.lastname: Li
authors.forename: Xiao-he
authors.initials: XH
authors.lastname: Xiao
mesh_terms: D000818:Animals; D002252:Carbon Tetrachloride Poisoning / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008107:Liver Diseases / Q000628:therapy*; D008297:Male; D010936:Plant Extracts / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012250:Rheum / Q000737:chemistry*
chemical_list: D010936:Plant Extracts