ABSTRACT
Long-term and excessive alcohol intake induces numerous biochemical and molecular alterations in hepatic tissue, which result in ethanol-related liver disease.1 Interference with vitamin A metabolism and its nutritional status is one of major alterations caused by alcohol.2,3 Lower hepatic vitamin A levels have been well documented in alcoholics.4,5 Several mechanisms have been proposed to explain how ethanol might interfere with retinoid metabolism in the liver (Figure 17.1). Ethanol has been found to lower the level of retinoids (retinyl ester, retinol, and retinoic acid) in the liver through increased catabolism of retinol and retinoic acid into more polar metabolites.4,6-8 Ethanol has been
seen to increase vitamin A mobilization from the liver to other organs, as evidenced by increased vitamin A concentration in extrahepatic tissue after chronic ethanol consumption.9,10 In addition, ethanol acts as a direct competitive inhibitor of retinol oxidation to retinoic acid in liver and other tissues. These alcohol-induced changes result in decreased hepatic levels of retinol and retinyl esters, which are precursors of retinoic acid, the most active form of vitamin A and a ligand for retinoid receptors. Retinoic acid plays an important
role in controlling cell growth, differentiation, and apoptosis and is of potential clinical interest in cancer chemoprevention and treatment.11 Therefore, interference with the retinoic acid metabolism by ethanol has important impacts on the etiology, prevention, and treatment of alcohol-related disease. In this chapter, recent studies on the ethanol interaction with retinoid homeostasis and signal transduction pathways are discussed.
