Hepatoprotective and antioxidant effects of the coffee diterpenes kahweol and cafestol on carbon tetrachloride-induced liver damage in mice.
The hepatoprotective effects of kahweol and cafestol, coffee-specific diterpenes, on the carbon tetrachloride (CCl(4))-induced liver damage as well as the possible mechanisms involved in these protections were investigated. Pretreatment with kahweol and cafestol prior to the administration of CCl(4) significantly prevented the increase in the serum levels of hepatic enzyme markers (alanine aminotransferase and aspartate aminotransferase) and reduced oxidative stress, such as reduced glutathione content and lipid peroxidation, in the liver in a dose-dependent manner. The histopathological evaluation of the livers also revealed that kahweol and cafestol reduced the incidence of liver lesions induced by CCl(4). Treatment of the mice with kahweol and cafestol also resulted in a significant decrease in the cytochrome P450 2E1 (CYP2E1), the major isozyme involved in CCl(4) bioactivation, specific enzyme activities, such as p-nitrophenol and aniline hydroxylation. Kahweol and cafestol exhibited antioxidant effects on FeCl(2)-ascorbate induced lipid peroxidation in a mouse liver homogenate, and on superoxide radical scavenging activity. These results suggest that the protective effects of kahweol and cafestol against the CCl(4)-induced hepatotoxicity possibly involve mechanisms related to their ability to block the CYP2E1-mediated CCl(4) bioactivation and free radical scavenging effects.
Lee
Kyung Jin
KJ
BK21 Project Team, Department of Pharmacy, College of Pharmacy, Research Center for Proteineous Materials, Chosun University, Kwangju, South Korea.
Choi
Jea Ho
JH
Jeong
Hye Gwang
HG
D000818:Animals; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002251:Carbon Tetrachloride / Q000633:toxicity*; D056486:Chemical and Drug Induced Liver Injury; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D004224:Diterpenes / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D016166:Free Radical Scavengers; D015971:Gene Expression Regulation, Enzymologic; D005978:Glutathione / Q000097:blood; D015227:Lipid Peroxidation; D008099:Liver / Q000473:pathology; D008107:Liver Diseases / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D015394:Molecular Structure; D013481:Superoxides
D000975:Antioxidants; D004224:Diterpenes; D016166:Free Radical Scavengers; D013481:Superoxides; C053401:kahweol; C053400:cafestol; D002251:Carbon Tetrachloride; D019392:Cytochrome P-450 CYP2E1; D005978:Glutathione