Study of agents for the prevention of the fatty liver produced by prolonged alcohol intake

Abstract

Summary To test their effectiveness in the prevention of alcoholic fatty liver, various agents were added to nutritionally adequate liquid diets, containing 36% of calories as ethanol or sucrose, fed to rats for 24 days. Large amounts of additives (α - tocopherol, 0.5; N,N'-dipheny 1- p -phenylenediamine (DPPD), 1.5; asparagine, 10 mg per cal), reported by others to protect against steatosis following a single large dose of ethanol were found to be ineffective in preventing the fatty liver produced by prolonged ethanol intake. Similarly, cyanocobalamin, 0.0005; methylene blue, 0.125; menadione, 0.5; carnitine, 1.0; and inositol, 2.5 mg per cal were ineffective. In contrast, partial protection was achieved with large amounts of DL-methionine or choline (2.5 and 5 mg per cal), with an average 70 to 80% reduction in triglyceride accumulation. This effect may be considered as pharmacological, since the basic diet already contained methionine, 1.5, and choline, 0.25 mg per cal, amounts of lipotropes reported to fully protect against steatosis from choline deficient diets. The incomplete protection also suggests that prolonged ethanol intake produces steatosis through effects other than or in addition to those related to lipotrope metabolism. A 72% decrease in hepatic triglyceride accumulation after ethanol was also obtained by isocaloric replacement of the regular long chain dietary triglycerides (41% of calories) by medium chain triglycerides (MCT).