Tissue-specific increases in endogenous all-trans retinoic acid: possible contributing factor in ethanol toxicity.
All-trans retinoic acid (atRA) is required for neurogenesis and dendritic growth in the hippocampus. The toxic effects of ethanol include developmental defects, cognitive dysfunction, and increased risk of cancer and have some similarities to the detrimental effects of excess atRA, the active form of vitamin A. It is therefore possible that disruption of atRA homeostasis would contribute to the deleterious effects of ethanol. However, previous work, using very high exogenous doses of retinol, found that ethanol toxicity led to decreased formation of atRA, apparently due to competitive inhibition of alcohol dehydrogenase, which is purportedly involved in the conversion of retinol to retinal. A new study, using assays that are highly sensitive for endogenous atRA, has reported that ethanol toxicity in mice actually increased atRA concentration in certain tissues, including brain hippocampus, apparently due to a mobilization of hepatic retinyl esters that led to increased retinol and atRA in specific tissues.
Wolf
George
G
Department of Nutritional Sciences and Toxicology, University of California, Berkeley, California, USA. nutritionreviews@ilsi.org
D000818:Animals; D001711:Biotransformation; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000209:etiology / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D051379:Mice; D011247:Pregnancy; D054840:Retinol-Binding Proteins, Cellular / Q000378:metabolism*; D014212:Tretinoin / Q000378:metabolism* / Q000494:pharmacology
D054840:Retinol-Binding Proteins, Cellular; D000431:Ethanol; D014212:Tretinoin