Arginine reverses ethanol-induced inflammatory and fibrotic changes in liver despite continued ethanol administration

We investigated the potential of arginine to reverse pathological changes i n alcohol-induced liver injury. Four groups (six rats/group) of male Wistar rats were fed a fish oil-ethanol diet for 6 (group 2) or 8 (group 1) weeks . Rats in group 3 were fed fish oil-ethanol for 6 weeks, after which they w ere administered arginine with fish oil-ethanol for an additional 2 weeks. Rats in group 4 were fed fish oil-dextrose for 8 weeks. Liver samples were analyzed for histopathology, lipid peroxidation, cytochrome P4502E1 activit y, nuclear factor-kappaB, and levels of messenger RNA for tumor necrosis fa ctor-alpha, cyclooxygenase-2, and inducible nitric oxide synthase. Concentr ations of endotoxin were measured in plasma. The most severe inflammation a nd fibrosis was detected in groups 1 and 2, as were the highest levels of e ndotoxin, lipid peroxidation, cytochrome P450 2E1 activity, activation of n uclear factor-kappaB, and mRNA levels for tumor necrosis factor-alpha, cycl ooxygenase-2, and inducible nitric oxide synthase. Plasma nitric oxide was also increased as was nitrotyrosine in liver. After arginine was administer ed, there was marked improvement in the pathological changes accompanied by decreased levels of endotoxin, lipid peroxidation, activation of nuclear f actor-kappaB, tumor necrosis factor-alpha, cyclooxygenase-2, inducible nitr ic oxide, and nitrotyrosine staining. The therapeutic effects of arginine a re probably secondary to increased levels of nitric oxide but other effects of arginine cannot be excluded.