The prevention of carbon tetrachloride-induced hepatotoxicity in mice by alpha-hederin: inhibiton of cytochrome P450 2E1 expression.
The protective effects of alpha-Hederin on carbon tetrachloride-induced hepatotoxicities were investigated in mice. Pretreatment with alpha-Hederin prior to the administration of carbon tetrachloride significantly prevented the increase in serum alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) activity and lipid peroxidation in a dose dependent manner. Hepatic glutathione levels and glutathione-S-transferase activities were not affected by pretreatment with alpha-Hederin alone but pretreatment with alpha-Hederin protects carbon tetrachloride-induced depletion of hepatic glutathione levels. The effects of alpha-Hederin on the cytochrome P450 (P450) 2E1, the major isozyme involved in carbon tetrachloride bioactivation were investigated. alpha-Hederin markedly decreased the P450 2E1-specific activities of p-nitrophenol and aniline hydroxylation in a dose-dependent manner. Consistent with these observations, the P450 2E1 expressions were also decreased, as determined by immunoblot analysis. These results demonstrate that treatment of mice with alpha-Hederin decreases the expression and activities of P450 2E1 enzyme, and reduces biotransformation of carbon tetrachloride, and diminished carbon tetrachloride-induced liver injury.
Jeong
H G
HG
Park
H Y
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D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity*; D019392:Cytochrome P-450 CYP2E1 / Q000096:biosynthesis*; D065691:Cytochrome P-450 CYP2E1 Inhibitors; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008099:Liver / Q000187:drug effects* / Q000201:enzymology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D009828:Oleanolic Acid / Q000031:analogs & derivatives*; D012503:Saponins / Q000008:administration & dosage / Q000627:therapeutic use*
D065691:Cytochrome P-450 CYP2E1 Inhibitors; D004365:Drugs, Chinese Herbal; D012503:Saponins; C010177:beta-hederin; D009828:Oleanolic Acid; D002251:Carbon Tetrachloride; D019392:Cytochrome P-450 CYP2E1