Effect of age on metabolic tolerance and hepatomegaly following chronic ethanol administration

Chronic consumption of ethanol often results in an increased rate of ethanol metabolism (metabolic tolerance) and in hepatomegaly. However, the extent of these changes is highly variable. We have found that these two phenomena are greatly influenced by age. We studied the effect of age on the development of metabolic tolerance and hepatomegaly and on the increase in hepatic oxygen consumption produced by chronic ethanol administration. The latter has been proposed to contribute to metabolic tolerance to ethanol. Ethanol was administered to female Sprague-Dawley rats with different initial ages (4, 6, 8, 11, and 17 weeks) for a 4-week period in a high-fat liquid diet. Control animals were pair-fed an isocaloric liquid diet in which ethanol was replaced with carbohydrate. Metabolic tolerance and hepatomegaly following chronic ethanol consumption were markedly dependent on the initial age of the animal, with young animals showing the largest increases. Although showing a similar general trend with age, the degree of metabolic tolerance was not linked proportionally with the degree of hepatomegaly. Perfused livers from young rats fed chronically with ethanol showed increases in ethanol metabolism and oxygen consumption, whereas no increase were observed in those from older animals. These findings support the hypothesis that an elevated rate of hepatic oxygen consumption contributes to metabolic tolerance. Total hepatic alcohol dehydrogenase activity was not increased by chronic ethanol consumption in any age group, demonstrating that an increase in the levels of this enzyme is not obligatory for metabolic tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)