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J.Health Sci., 55(3), 356-362, 2009

Hepatic Cytochrome P450 2E1 Level Rather Than Cecal Condition Contributes to Induction of Early Stage of the Alcoholic Liver Damage in Rats

Naoto Hashimoto,*, a Hiroyuki Sekiguchi,a Akira Masunaka,a Katsuichi Saito,a Hiroaki Yamauchi,a Takahiro Noda,a Kyu-Ho Han,b and Michihiro Fukushimab

aMemuro Upland Farming Research Station, National Agricultural Research Center for Hokkaido Region, Shinsei, Memuro, Kasai, Hokkaido 082-0081, Japan and bDepartment of Animal Science, Obihiro University of Agriculture and Veterinary Medicine, Inada, Obihiro, Hokkaido 080-8555, Japan

Intestinal condition and ethanol toxicity have been discussed as predictors of alcoholic liver damage. In this study, we investigated the association of hepatic antioxidant enzymes and cecal condition, including intestinal bacteria estimated by terminal restriction fragment length polymorphism (T-RFLP), in the early stage of alcoholic fatty liver. Three liquid isocaloric diets, control (CT) diet, ethanol (ET) diet, or ethanol diet including modified beet fiber (MBF), were prepared and administered to rats for 4 weeks. At 4 weeks, the plasma alanine aminotransferase (ALT) levels in the ET group were higher and that in MBF groups tended to be higher than the CT group, but endotoxin was not detected in the portal vein in any of the samples. The hepatic thiobarbituric acid reactive substances (TBARS) concentration in the MBF group was higher than that in the CT group. Hepatic cytochrome P450 2E1 (CYP2E1) was induced in ethanol-fed rats. The hepatic catalase levels in the ET and MBF groups were lower than that in the CT group. The hepatic superoxide dismutase-2 (SOD-2) level did not differ among the groups. Plasma ALT level and/or hepatic TBARS level correlated positively with CYP2E1 and negatively with catalase level and SOD-2 level. Indicators of cecal condition, including the bacterial population estimated by T-RFLP, may not give any explanation for the hepatic damage. In conclusion, the hepatic CYP2E1 induced by ethanol, rather than the cecal conditions, may influence the early stage of alcoholic hepatic damage in rats; hepatic catalase may provide protective effects.