Enhancement of ethanol-induced lipid peroxidation in rat liver by lowered carbohydrate intake.

In order to investigate the effect of carbohydrate intake on ethanol-induced lipid peroxidation and cytotoxicity, rats were maintained on four different test diets, a medium-carbohydrate (carbohydrate intake, 8.4 g/day/rat on average), a low-carbohydrate (carbohydrate intake, 2.8 g/day/rat on average), an ethanol-containing medium-carbohydrate (carbohydrate and an ethanol intake, 8.4 and 2.9 g/day/rat on average, respectively), and an ethanol-containing low-carbohydrate diet (2.8 and 2.9 g/day/rat on average, respectively). Ethanol and the low-carbohydrate diet each increased the liver malondialdehyde content, but the combined effect of both (ethanol-containing low-carbohydrate diet) was much more prominent than either alone. The degree of increase in malondialdehyde content almost paralleled the activity of the microsomal ethanol oxidizing system. Both the low-carbohydrate and the ethanol-containing low-carbohydrate diets decreased the liver glutathione content, but ethanol combined with the medium-carbohydrate diet had no effect on the content. Ethanol treatment increased the liver triglyceride content only when combined with the low-carbohydrate diet. The rate of NADPH-dependent microsomal malondialdehyde formation was much higher in microsomes from rats maintained on the ethanol-containing low-carbohydrate diet than in those from rats on the ethanol-containing medium-carbohydrate diet, indicating that lowered carbohydrate intake augments ethanol-induced malondialdehyde accumulation in the liver by enhancing the rate of lipid peroxidation. In addition, when incubated with red blood cells in the presence of NADPH, microsomes from rats fed the ethanol-containing low-carbohydrate diet caused marked hemolysis, which was prevented by the addition of 5 mM glutathione to the incubation system. Furthermore, addition of 50 mM ethanol to the reaction system greatly accentuated the hemolysis. These results suggest that lowered carbohydrate intake at the time of ethanol consumption potentiates ethanol cytotoxicity by enhancing ethanol-induced lipid peroxidation.