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.

在医疗法律实践中进行的血液酒精浓度估算中，个体间和个体内乙醇消除能力的差异是一个重要问题。反复饮酒引起的酶诱导是引起酒精代谢个体差异的著名机制之一。此外，短时间接触产生的酒精代谢加速增加，称为SIAM（酒精代谢迅速增加，瑟曼等人，1979），被认为是另一种机制。在这种SIAM现象中，由于急性摄入高浓度酒精，耗氧量和酒精代谢加速上升。本研究的目的是探讨SIAM现象的机制，并了解SIAM现象与乙醇代谢个体差异之间的关系。此外，还详细研究了SIAM对乙醛和乙酸盐处置的影响。其结果，得到了再现性良好地发生SIAM现象的条件，可知血液中醋酸盐浓度随着酒精消除率的加速增加而增加。这些结果表明血液醋酸盐的稳态浓度可以作为SIAM的指标。血液醋酸盐的这种变化成为SIAM研究的新知识。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现象期间没有变化。然而，某些细胞色素的含量会随着SIAM现象发生变化。进一步的研究正在进行中。