NITRIC-OXIDE PRODUCTION IN EXPERIMENTAL ALCOHOLIC LIVER-DISEASE IN THE RAT - ROLE IN PROTECTION FROM INJURY

Background & Aims: Regulation of blood flow and oxygen supply are impo rtant pathogenetic factors in alcoholic liver disease. Because nitric oxide may have an important role, its effects on alcoholic liver injur y were investigated. Methods: Rats were fed ethanol intragastrically w ith either saturated fat or corn oil. Spontaneous production of NO by liver nonparenchymal cells was compared in the two dietary groups. Two additional groups of rats fed corn oil and ethanol were treated with either an NO inhibitor (L-NAME) or supplemented with L-arginine. Liver pathology and plasma NO production were evaluated. Results: In the co rn oil and ethanol group, a progressive decrease in liver nonparenchym al cell NO production and increased plasma NO levels were associated w ith liver injury. Reduced nicotinamide adenine dinucleotide phosphate diaphorase staining showed increased centrilobular staining of hepatoc ytes in the corn oil and ethanol group and L-NAME-treated group. Moreo ver, L-NAME increased the severity, whereas L-arginine supplementation completely prevented liver injury. In the saturated fat and ethanol g roup, in which there was no liver injury, the levels of NO2- in nonpar enchymal supernatant were 5-10-fold higher than in the corn oil and et hanol group. Conclusions: Decreased NO production by nonparenchymal ce lls may contribute to liver injury in ethanol-fed rats, and the compen satory increase in hepatocyte NO production may contribute to centrilo bular liver injury.