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Mechanism of Swift lncrease in Alcohol Metabolism and Individual Difference of its metabolism

酒精代谢快速增加的机制及其代谢的个体差异

基本信息

批准号：
18590636
负责人：
FUJIMIYA Tatsuya
金额：
$ 2.46万
依托单位：
Yamaguchi University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

项目摘要

In the estimation of blood-alcohol-concentration performed in Medico-Legal practice, the inter- and intra-individual difference of ethanol elimination capacity is an important problem. The enzyme induction with repeated alcohol drinking is one of famous mechanisms to evoke an individual difference in alcohol metabolism. In addition, the accelerative increase of the alcohol metabolism produced for a short time exposure, called SIAM (Swift Increase in Alcohol Metabolism, Thurman and others, 1979), is thought to be another mechanism. In this SIAM phenomenon oxygen consumption and alcohol metabolism rise accelerative by acute administration of high-concentration alcohol. The purpose of this study is to examine the mechanism of SIAM phenomenon and to know the relationship between this SIAM phenomenon and individual difference of ethanol metabolism. Furthermore, the effects of SIAM to the disposition of acetaldehyde and acetate are studied in detail. As a result, the conditions which SIAM phenomenon occurs with sufficient reproducibility were acquired, and it was found that the blood concentration of acetate increases with accelerative increase of an alcoholic elimination rate. These results indicate that the steady-state concentration of blood acetate serves as an index of SIAM. This change of blood acetate became new knowledge for SIAM study. This experimental condition and pharmacokinetic data were used for biochemical studies. Consequently, contents of alcohol dehydrogenase and aldehyde dehydrogenase did not change during the SIAM phenomenon. However, content of some cytochrome change with SIAM phenomenon. Further study is being performed.

在法医实践中进行血液酒精浓度的估计时，个体间和个体内乙醇清除能力的差异是一个重要的问题。反复饮酒引起的酶诱导是引起酒精代谢个体差异的重要机制之一。此外，短时间暴露产生的酒精代谢加速增加，称为SIAM（酒精代谢迅速增加，瑟曼等，1979），被认为是另一种机制。在这种SIAM现象中，急性给予高浓度酒精可加速氧耗和酒精代谢的增加。本研究的目的是探讨SIAM现象的发生机制，以及这种现象与乙醇代谢个体差异的关系。此外，还详细研究了SIAM对乙醛和乙酸的降解效果。结果，获得了SIAM现象以足够的再现性发生的条件，并且发现乙酸盐的血液浓度随着酒精消除速率的加速增加而增加。这些结果表明，稳态血醋酸盐浓度作为SIAM的指标。血醋酸盐的这种变化为SIAM的研究提供了新的认识。该实验条件和药代动力学数据用于生化研究。因此，乙醇脱氢酶和乙醛脱氢酶的含量在SIAM现象中没有变化。但某些细胞色素的含量变化与SIAM现象有关。正在进行进一步研究。