Pronounced hepatic free radical formation precedes pathological liver injury in ethanol-fed rats

Background: The role of free radicals in alcoholic liver injury remains unc ertain. These experiments were conducted to measure radical formation in ra ts that were fed alcohol along with either fish oil or saturated fats, whic h cause different types of liver pathology. Methods: Liquid diets containing alcohol or isocaloric dextrose were admini stered to rats by intragastric infusion for 2 weeks. Radical intermediates detected by spin trapping were measured in bile. Results: In rats that were fed alcohol plus fish oil, biliary concentration s of trapped radicals, which most likely originated from lipids, were G-fol d higher than in controls that were fed fish oil plus dextrose. High rates of radical formation persisted 24 hr after alcohol withdrawal, when all alc ohol had been metabolized. In contrast, diets containing alcohol and medium chain triglycerides did not stimulate lipid radical formation. Conclusions: High rates of lipid radical formation were observed only in ra ts that were fed alcohol in combination with a fish oil diet, and a persist ent flux of radical formation continued after alcohol withdrawal. These rad ical phenomena precede serious liver pathology, which develops after longer periods of fish oil plus alcohol diets.