Ethanol toxicity : lipid and carbohydrate metabolism, ethanol in pregnancy and the ftal alcohol syndrome.

Abstract

Ethanol is absorbed by diffusion across the gastric and intestinal mucosa.Following absorption, ethanol is mainly metabolized in the liver where cytosolic alcohol dehydrogenase and mitochondrial aldehyde dehydrogenase are the principal enzymes of ethanol oxidation. Hepatic metabolism of ethanol leads to an increased formation of NADH and acetaldehyde which are the factors directly responsible for most of the metabolic disturbances produced by ethanol. Almost all lipid metabolism pathways are affected by ethanol, and hyperlipemia and fat accumulation in the liver are the most common disturbances. Several mechanisms contribute to these conditions but the ethanol effects of enhancing the arrival of lipids to the liver and decreasing their further disposition seem to be the most important. Ethanol effects on carbohydrate metabolism are also very diverse, producing either hyperglycemia or hypoglycemia depending on the availability of glycogen stores. Ethanol decreases liver gluconeogenetic activity by siphoning substrates which are converted to their reduced form. Alcohol ingestion during pregnancy may produce the fetal alcohol syndrome which causes retarded growth and abnormalities in fetal development. Animal models for this syndrome have been developed using different species. In the rat, 25% ethanol in the drinking water during pregnancy provides a daily total caloric intake similar to that of pregnant controls but causes weight reduction in both mother and fetus. Blood glucose levels are preserved in the alcoholic rat mother but liver glycogen is decreased and blood ketone bodies are augmented and these parameters are significantly affected in the fetus.