Haseba Takeshi, Sugimoto Junichi, Sato Shigeo, Abe Yuko, Ohno Youkichi
Department of Legal Medicine, Nippon Medical School, Bunkyo-ku, Tokyo 113-8602, Japan.
Metabolism. 2008 Dec;57(12):1753-9. doi: 10.1016/j.metabol.2008.09.003.
We recently reported that the maturation of whisky prolongs the exposure of the body to a given dose of alcohol by reducing the rate of alcohol metabolism and thus lowers the blood acetaldehyde level (Alcohol Clin Exp Res. 2007;31:77s-82s). In this study, administration of the nonvolatile fraction of whisky was found to lower the concentration of acetaldehyde in the blood of mice by depressing alcohol metabolism through the inhibition of liver alcohol dehydrogenase (ADH). Four of the 12 phenolic compounds detected in the nonvolatile fraction (caffeic acid, vanillin, syringaldehyde, ellagic acid), the amounts of which increase during the maturation of whisky, were found to strongly inhibit mouse ADH 1 (class I). Their inhibition constant values for ADH 1 were 0.08, 7.9, 15.6, and 22.0 mumol/L, respectively, whereas that for pyrazole, a well-known ADH inhibitor, was 5.1 mumol/L. The 2 phenolic aldehydes and ellagic acid exhibited a mixed type of inhibition, whereas caffeic acid showed the competitive type. When individually administered to mice together with ethanol, each of these phytophenols depressed the elimination of ethanol, thereby lowering the acetaldehyde concentration of blood. Thus, it was demonstrated that the enhanced inhibition of liver ADH 1 due to the increased amounts of these phytophenols in mature whisky caused the depression of alcohol metabolism and a consequent lowering of blood acetaldehyde level. These substances are commonly found in various food plants and act as antioxidants and/or anticarcinogens. Therefore, the intake of foods rich in them together with alcohol may not only diminish the metabolic toxicity of alcohol by reducing both the blood acetaldehyde level and oxidative stress, but also help limit the amount of alcohol a person drinks by depressing alcohol metabolism.
我们最近报道，威士忌的陈酿通过降低酒精代谢速率延长了人体对给定剂量酒精的接触时间，从而降低了血液中乙醛的水平（《酒精临床与实验研究》。2007年；31:77s - 82s）。在这项研究中，发现给予威士忌的非挥发性部分可通过抑制肝脏乙醇脱氢酶（ADH）来抑制酒精代谢，从而降低小鼠血液中乙醛的浓度。在非挥发性部分检测到的12种酚类化合物中有4种（咖啡酸、香草醛、丁香醛、鞣花酸），其含量在威士忌陈酿过程中会增加，它们被发现能强烈抑制小鼠ADH 1（I类）。它们对ADH 1的抑制常数分别为0.08、7.9、15.6和22.0 μmol/L，而著名的ADH抑制剂吡唑的抑制常数为5.1 μmol/L。这两种酚醛和鞣花酸表现出混合型抑制，而咖啡酸表现出竞争型抑制。当这些植物酚与乙醇一起单独给予小鼠时，它们各自都会抑制乙醇的消除，从而降低血液中乙醛的浓度。因此，已证明成熟威士忌中这些植物酚含量的增加导致肝脏ADH 1抑制增强，从而抑制了酒精代谢并导致血液中乙醛水平降低。这些物质在各种食用植物中普遍存在，并作为抗氧化剂和/或抗癌剂发挥作用。因此，摄入富含这些物质的食物与酒精一起，不仅可以通过降低血液中乙醛水平和氧化应激来降低酒精的代谢毒性，还可以通过抑制酒精代谢来帮助限制一个人饮酒的量。
