Alcohol and Retinoids

Abstract

This article represents the proceedings of a symposium at the 2000 ISBRA Meeting in Yokohama, Japan. The chairs were Hirokazu Yokoyama and David Crabb. The presentations were (1) Roles of vitamin A, retinoic acid, and retinoid receptors in the expression of liver ALDH2, by J. Pinaire, R. Hasanadka, M. Fang, and David W. Crabb; (2) Alcohol, vitamin A, and ␤-carotene: Adverse interactions, by M. A. Leo and Charles S. Lieber; (3) Retinoic acid, hepatic stellate cells, and Kupffer cells, by Hidekazu Tsukamoto, K. Motomura, T. Miyahara, and M. Ohata; (4) Retinoid storage and metabolism in liver, by William Bosron, S. Sanghani, and N. Kedishvili; (5) Characterization of oxidation pathway from retinol to retinoic acid in esophageal mucosa, by Haruko Shiraishi, Hirokazu Yokoyama, Michiko Miyagi, and Hiromasa Ishii; and (6) Ethanol in an inhibitor of the cytosolic oxidation of retinol in the liver and the large intestine of rats as well as in the human colon mucosa, by Ina Bergheim, Ina Menzl, Alexandr Parlesak, and Christiane Bode.

Evaluation of Aldehyde Dehydrogenase 1 Promoter Polymorphisms Identified in Human Populations

“…ALDH1A1 eliminates acetaldehyde, a potentially pharmacological and neurotoxic agent, from the nervous system (Brien and Loomis, 1983). ALDH1A1 has also been implicated in the synthesis of retinoic acid, an important agent in many developmental processes and an essential precursor in vitamin A production (Crabb et al, 2001). In fact, it has been suggested that acetaldehyde and retinaldehyde competition may be a contributing factor in vitamin A abnormalities observed in alcoholics (Ambroziak et al, 1999).…”

Hepatotoxicity of alcohol‐induced polar retinol metabolites involves apoptosis via loss of mitochondrial membrane potential

“…Unfortunately, high doses of vitamin A (>100,000 IU/day) are hepatotoxic and can even lead to the development of liver cirrhosis when taken over a period of weeks or months (9,10). Chronic alcohol consumption has been shown to further enhance this intrinsic hepatotoxicity, and it has been demonstrated that liver damage can occur with vitamin A doses as low as 7,500-10,000 IU/day, which is well in the range of doses commonly found in commercial supplements (3,6). An explanation for the enhanced vitamin A hepatotoxicity could be that alcohol-induced microsomal enzymes may generate high amounts of toxic metabolites from various retinoids that add to alcohol-induced liver injury (4).…”

“…Interference with vitamin A turnover is particularly important, since excess alcohol intake leads to a striking depletion of hepatic vitamin A stores both in experimental animals (3) and in alcoholics (4). In humans, vitamin A deficiency can cause night blindness (5), sexual dysfunction (6), and has been associated with birth defects (7) as well as with alcohol-mediated carcinogenesis (8).…”

Protective effect of some vitamins against the toxic action of ethanol on liver regeneration induced by partial hepatectomy in rats

“…Since the 80's the equilibrium between the generation of free radicals and the endogenous antioxidant mechanisms have been recognized. It has been established that this balance can be altered during oxidative stress induced by different xenobiotics and it can also be reestablished when antioxidant compounds like ascorbic acid (vitamin C), alpha-tocopherol (vitamin E), or b-carotene (vitamin A) are administrated [41,42] . The results of this study ( Figure 2) support this observation, since the 3 vitamins showed a protective effect against the generation of hydroxyethyl radicals generated by the ethanol; although the most significant efficiency was with vitamin C and E, where the hepatic regeneration reached 94% and 96% respectively (Table 2).…”