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

Background: The role of free radicals in alcoholic liver injury remains uncertain. These experiments were conducted to measure radical formation in rats that were fed alcohol along with either fish oil or saturated fats, which cause different types of liver pathology. Methods: Liquid diets containing alcohol or isocaloric dextrose were administered 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 concentrations of trapped radicals, which most likely originated from lipids, were 6-fold higher than in controls that were fed fish oil plus dextrose. High rates of radical formation persisted 24 hr after alcohol withdrawal, when all alcohol 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 rats that were fed alcohol in combination with a fish oil diet, and a persistent flux of radical formation continued after alcohol withdrawal. These radical phenomena precede serious liver pathology, which develops after longer periods of fish oil plus alcohol diets.