Large Dose Means Significant Effect?-Investigation of the hepatoprotective effects and dose-effect relationship of Chi-Dan-Tui-Huang decoction on alpha-naphthylisothiocyanate-induced acute cholestatic hepatitis in rats
Over-dose use of traditional Chinese medicines(TCMs)has attracted more and more attentions in recent years.Exploring the rational and scientific dose of TCMs to be used in clinical settings has become much more imperative.The present study was designed to investigate the protective effects of Chi-Dan-Tui-Huang decoction(CDTHD)on alpha-naphthylisothiocyanate(ANIT)-induced acute cholestatic hepatitis in rats,and to try to explore the dose-effect relationship as well as the relationship between large dose and toxicity.Cholestatic hepatitis was induced by intragastric administration of ANIT 60 mg/kg to rats for 2days.Then,a range of CDTHD doses(5.4,10.8,21.6,43.2 and 81 g/kg·d)were intragastrically administered to ANIT-treated rats twice each day for 3 days.Two days after CDTHD was given,the protective effects against cholestatic hepatitis were investigated by examining the folloeing parameters:body weights of rats,morphological and histopathological liver changes,malonyldialdehyde(MDA)contents and superoxide dismutase(SOD)activities,and the levels of serum biomarkers including alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBIL)and direct bilirubin(DBIL)alkaline phosphatase(ALP),and γ-glutamyl transpeptidase(γ-GT).Further more,the dose-effect relationship was investigated with the application of correspondence analysis.The results showed that CDTHD exhibited a significant hepatoprotective effect on injured liver,reversing adverse biochemical and histopathological changes.These protective effects were acieved in a dose-dependent manner as CDTHD in range of 21.6-81 g/kg·d could dose-dependently ameliorate ANIT-induced acute cholestatic hepatitis in rats.In the tested range of doses,CDTHD did not show any toxic effects with increases of dose and time.These results are consistent with the histopathological observations and the determination of serum levels of biomarkers of liver injury.This study provides useful data for studying the dose-effect relationship and the rational and safe use of TCMs in clinical srttings.
Acute cholestatic hepatitis ANIT Hepatoprotective effect Dose-effect relationship Correspondence analysis
LIU shu-xian ZHAO yan-ling SUN zhi-yong WANG jia-bo Liu tian-tian SUN xiao-jiao JIA lei LI rui-sheng LI jian-yu WANG li-fu XIAO xiao-he
302 Hospital of People”s Liberation Army,Beijing,100039,China;Pharmacy College,Chengdu University of 302 Hospital of People”s Liberation Army,Beijing,100039,China Pharmacy College,Chengdu University of Traditional Chinese Medicine,Chengdu,611137,China School of Chinese Medicine,The University of Hong Kong,Hong Kong,999077,China
国内会议
成都
英文
280-297
2013-11-01（万方平台首次上网日期，不代表论文的发表时间）