Epigallocatechin-3-Gallate Ameliorates Alcohol-Induced Liver Injury in Rats

Abstract

Endotoxemia is a common event in alcoholic liver disease. Elevated intestinal permeability is the major factor involved in the mechanism of alcoholic endotoxemia and the pathogenesis of alcoholic liver disease. This study examined the effect of epigallocatechin-3-gallate (EGCG) on alcohol-induced gut leakiness, and explored the related mechanisms involved in its protection against alcohol-induced liver injury in rats. Four groups of female Sprague-Dawley rats were studied. Alcohol and alcohol/EGCG groups rats received fish oil along with alcohol daily via gastrogavage for 6 weeks, and dextrose and dextrose/EGCG groups rats were given fish oil along with isocaloric dextrose instead of alcohol. The dextrose/EGCG and alcohol/EGCG groups received additional treatment of EGCG (100mg.kg -1 body weight) daily intragastrically by gavage. Intestinal permeability was assessed by urinary excretion of lactulose and mannitol (L/M ratio). Liver injury was evaluated histologically and by serum alanine aminotransferase (ALT). Plasma endotoxin and serum tumor necrosis factor-α (TNF-α) levels were assayed; liver malondialdehyde (MDA) contents determined. CD14 and inflammatory factors, such as TNF-α, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) mRNAs in the liver were analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). Rats given fish oil plus alcohol had gut leakiness (L/M ratio was increased), which was associated with both endotoxemia and liver injury. The above responses were accompanied by increased CD14, TNF-α, COX-2 and iNOS mRNA expressions in the liver. EGCG supplementation partly blocked the gut leakiness, reduced endotoxemia and lipid peroxidation, and blunted the elevated expressions of CD14, TNF-α, COX-2 and iNOS, all of which were associated with improved liver injury. These results show that EGCG can

Atorvastatin attenuates ethanol-induced hepatotoxicity via antioxidant and anti-inflammatory mechanisms

“…TNF-α is one of the most important inflammatory mediator produced in the initial step of several models of hepatotoxicity. Also, the role of nitric oxide in hepatotoxicity was confirmed by showing increased level of stable metabolites of nitric oxide including nitrites and nitrates ( 3 5 7 8 29 ). Indeed, nitric oxide in combination with oxygen radicals could form peroxynitrite that is known as the most potent oxidants that contribute in oxidative damage to cells and tissues.…”

“…Damage to lipid membrane and DNA due to oxidative stress could finally lead to cell death and tissue damage. On the other hand, alcohol-induced oxidative stress in liver tissue could promote hepatic inflammation ( 8 ). Another suggested mechanism for ethanol hepatotoxicity is the increased expression of inflammatory mediators such as TNF-α.…”

“…Several studies suggested using of antioxidants such as vitamins A or E ( 1 4 ), pentoxifylline (as an inhibitor of TNF-α), anti- TNF-α antibody and other cytokines ( 7 ), grape Vitis vinifera L . leaf as an antioxidant, glutathione (GSH), vitamin C ( 5 ), epigallocatechin-3-gallate ( 8 ), N-acetyl-L-cysteine ( 2 ), methanolic extract (ME) of Acorus calamus ( 9 ), aqueous extract of fenugreek ( Trigonella foenum graecum ) seeds ( 10 ), and quercetin ( 11 ) for attenuating of ethanol hepatotoxicity.…”

Better Management of Alcohol Liver Disease Using a ‘Microstructured Synbox’ System Comprising L. plantarum and EGCG

“…Alcohol induces damage by building up endotoxin mediated oxidative stress in the cellular constituents of the tissue. Catechins including EGCG have been demonstrated previously by us [11, 12] and others [13, 14] to attenuate alcoholic liver injury by creating an antioxidant- oxidant balance in the hepatic tissues. ALD is also accompanied by elevated intestinal permeability which can be abridged by probiotic administration.…”

Hepato- and neuro-protective effects of watermelon juice on acute ethanol-induced oxidative stress in rats

“…The protective effects of antioxidant rich natural compounds against different toxicant mediated tissue injury has been identified in many studies [13] , [14] , [15] . In specific, numerous studies have demonstrated the protective effects of antioxidants such as pumpkin oil [16] , resveratrol [17] , curcumin [18] , quercetin [19] and epigallocatechin-3-gallate [20] against alcohol induced tissue injury.…”