Abstract: Endotoxemia is a common event in alcoholic liver disease. Elevated intestinalpermeability is the major factor involved in the mechanism of alcoholic endotoxemia andthe pathogenesis of alcoholic liver disease. This study examined the effect ofepigallocatechin-3-gallate (EGCG) on alcohol-induced gut leakiness, and explored therelated mechanisms involved in its protection against alcohol-induced liver injury in rats.Four groups of female Sprague-Dawley rats were studied. Alcohol and alcohol/EGCGgroups rats received fish oil along with alcohol daily via gastrogavage for 6 weeks, anddextrose and dextrose/EGCG groups rats were given fish oil along with isocaloric dextroseinstead of alcohol. The dextrose/EGCG and alcohol/EGCG groups received additionaltreatment of EGCG (100mg.kg-1 body weight) daily intragastrically by gavage. Intestinalpermeability was assessed by urinary excretion of lactulose and mannitol (L/M ratio). Liverinjury was evaluated histologically and by serum alanine aminotransferase (ALT). Plasmaendotoxin and serum tumor necrosis factor-α (TNF-α) levels were assayed; livermalondialdehyde (MDA) contents determined. CD14 and inflammatory factors, such asTNF-α, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) mRNAs inthe liver were analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). Ratsgiven fish oil plus alcohol had gut leakiness (L/M ratio was increased), which wasassociated with both endotoxemia and liver injury. The above responses were accompaniedby increased CD14, TNF-α, COX-2 and iNOS mRNA expressions in the liver. EGCGsupplementation partly blocked the gut leakiness, reduced endotoxemia and lipidperoxidation, and blunted the elevated expressions of CD14, TNF-α, COX-2 and iNOS, allof which were associated with improved liver injury. These results show that EGCG can block alcohol-induced gut leakiness, reduce endotoxemia, and inhibit inflammatory factors expressions in the liver, thereby ameliorates alcohol-induced liver injury.
Keywords: epigallocatechin-3-gallate; alcohol-induced liver injury; intestinal permeability; endotoxemia; CD14; cyclooxygenase-2; inducible nitric oxide synthase.
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Yuan, G.; Gong, Z.; Zhou, X.; Zhangq, P.; Sun, X.; Li, X. Epigallocatechin-3-Gallate Ameliorates Alcohol-Induced Liver Injury in Rats. Int. J. Mol. Sci. 2006, 7, 204-219.
Yuan G, Gong Z, Zhou X, Zhangq P, Sun X, Li X. Epigallocatechin-3-Gallate Ameliorates Alcohol-Induced Liver Injury in Rats. International Journal of Molecular Sciences. 2006; 7(7):204-219.
Yuan, Guangjin; Gong, Zuojiong; Zhou, Xiaorong; Zhangq, Pin; Sun, Xiaomei; Li, Xi. 2006. "Epigallocatechin-3-Gallate Ameliorates Alcohol-Induced Liver Injury in Rats." Int. J. Mol. Sci. 7, no. 7: 204-219.