PMID- 22103766 OWN - NLM STAT- MEDLINE DCOM- 20120531 LR - 20131121 IS - 1744-5116 (Electronic) IS - 1388-0209 (Linking) VI - 50 IP - 3 DP - 2012 Mar TI - Evaluation of the liver protection and toxicity of Da-Huang-Zhe-Chong pill in rats. PG - 344-50 LID - 10.3109/13880209.2011.604333 [doi] AB - CONTEXT: 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. MATERIALS AND 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. DISCUSSION AND CONCLUSION: 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. FAU - Xing, Xiao-yan AU - Xing XY AD - China Military Institute of Chinese Materia Medica, 302 Military Hospital of China, Beijing, PR China. FAU - Zhao, Yan-ling AU - Zhao YL FAU - Jia, Lei AU - Jia L FAU - Kong, Wei-jun AU - Kong WJ FAU - Zhong, Yan-wei AU - Zhong YW FAU - Wang, Jia-bo AU - Wang JB FAU - Zhang, Ping AU - Zhang P FAU - Ren, Hui-ling AU - Ren HL FAU - Xiao, Xiao-he AU - Xiao XH LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20111121 PL - England TA - Pharm Biol JT - Pharmaceutical biology JID - 9812552 RN - 0 (Dahuang Zhechong pill) RN - 0 (Drugs, Chinese Herbal) RN - 0 (Protective Agents) RN - CL2T97X0V0 (Carbon Tetrachloride) SB - IM MH - Animals MH - Carbon Tetrachloride/toxicity MH - Dose-Response Relationship, Drug MH - Drugs, Chinese Herbal/administration & dosage/*pharmacology/toxicity MH - Female MH - Injections, Intraperitoneal MH - Liver Diseases/physiopathology/*prevention & control MH - Liver Function Tests MH - Male MH - Protective Agents/administration & dosage/*pharmacology/toxicity MH - Rats MH - Rats, Sprague-Dawley MH - Time Factors EDAT- 2011/11/23 06:00 MHDA- 2012/06/01 06:00 CRDT- 2011/11/23 06:00 PHST- 2011/11/23 06:00 [entrez] PHST- 2011/11/23 06:00 [pubmed] PHST- 2012/06/01 06:00 [medline] AID - 10.3109/13880209.2011.604333 [doi] PST - ppublish SO - Pharm Biol. 2012 Mar;50(3):344-50. doi: 10.3109/13880209.2011.604333. Epub 2011 Nov 21.