Allopurinol prevents early alcohol-induced liver injury in rats

Free radical formation caused by chronic ethanol administration could activ ate transcription factors such as nuclear factor-kappa B (NF-kappa B), whic h regulates production of inflammatory cytokines. Xanthine oxidase is one p otential source of reactive oxygen species. Therefore, the purpose of this study is to determine whether allopurinol, a xanthine oxidase inhibitor and scavenger of free radicals, would affect free radical formation, NF-kappa B activation, and early alcohol-induced liver injury in rats. Male Wistar r ats were fed a high-fat diet with or without ethanol (10-16 g/kg/day) conti nuously for up to 4 weeks with the Tsukamoto-French enteral protocol. Eithe r allopurinol or saline vehicle was administered daily. Allopurinol had no effect on body weight or the cyclic pattern of ethanol in urine. Mean urine ethanol concentrations were 271 +/- 38 and 252 +/- 33 mg/dl in ethanol- an d ethanol + allopurinol-treated rats, respectively. In the control group, s erum aspartate aminotransferase and alanine aminotransferase levels were si milar to 40 I.U./I and 25 U/I, respectively. Administration of enteral etha nol for 4 weeks increased serum transaminases similar to 5-fold. Allopurino l blunted these increases significantly by similar to 50%. Ethanol treatmen t also caused severe fatty infiltration, mild inflammation, and necrosis. T hese pathological changes also were blunted significantly by allopurinol. F urthermore, enteral ethanol caused free radical adduct formation, values th at were reduced by similar to 40% by allopurinol. NF-kappa B binding was mi nimal in the control group but was increased significantly nearly 2.5-fold by ethanol. This increase was blunted to similar values as control by allop urinol. These results indicate that allopurinol prevents early alcohol-indu ced liver injury, most likely lay preventing oxidant-dependent activation o f NF-kappa B.