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The complex interactions between the metabolism of retinoids and ethanol have been reported for a long time. Clinically, chronic ethanol consumption leads to vitamin A deficiency but also to enhanced toxicity of vitamin A and beta-carotene when supplemented. Changes in retinol metabolism due to alcohol may have a pathophysiological impact in both alcoholic liver disease and alcohol associated cancer as retinoic acid, the most active form of vitamin A, is an important regulator of normal epithelial cell growth, function, and differentiation. Under normal conditions, ingested retinol is metabolised to retinaldehyde via cytosolic alcohol dehydrogenase (ADH), microsomal retinol dehydrogenase (three types), and several types of cytosolic retinol dehydrogenases, and retinaldehyde is further oxidised to retinoic acid via aldehyde dehydrogenase (ALDH). Retinoic acid binds to retinoic acid receptors (RAR), initiating intracellular signal transduction leading to a cascade of events and finally to a decrease in cell regeneration. The main molecular action of retinoic acid involves either transactivation through direct binding to retinoic acid response elements (RARE) in target gene promoters, thereby transcriptionally activating a series of genes with distinct antiproliferative activity, or transrepression of activator protein (AP-1) and regulation of apoptosis. It is not surprising that this complex interaction between ethanol and metabolism of retinoids occurs as both substrates share common pathways, namely (a) ADH, (b) ALDH, and (c) cytochrome P4502E1 (CYP2E1).
It has been shown that chronic ethanol consumption decreases hepatic retinol and retinoic acid concentrations due to various mechanisms including, increased mobilisation of retinyl esters to extrahepatic tissues and enhanced hepatic metabolism of retinol and retinoic acid to polar metabolites, predominantly via induced CYP2E1.1 ,2These …