Fundamental study on the estimation of blood concentration of ethanol and its metabolites

在日本，由于乙醛脱氢酶(ALDH2)活性的部分缺陷，导致许多人在饮酒时出现潮红反应，从而积聚了乙醛。我们研究了血液乙醇水平对乙醛和乙酸酯在氰胺处理和不处理的情况下的影响，氰胺是ALDH2的抑制剂。以兔为实验对象。以1.0g/kgBW或2.0g/kgBW静脉注射乙醇生理盐水20min，然后恒速输注(0.25g/kg/小时)。在4小时和8小时时，输注速度增加到0.5g/kg/小时，持续1小时。用顶空气相色谱法测定血液中乙醇、乙醛和乙酸盐的浓度。我们发现血液中乙醇浓度在2小时内达到稳定状态。血液乙醛浓度随着血液中乙醇浓度的升高而呈尖峰状升高，在升高约1小时后达到稳定状态。乙醛的浓度变化与血液中乙醇浓度成正比，提示乙醛毒性可能随乙醇量的增加而增加。我们还发现，血醋酸盐浓度在给药后2小时内达到稳定状态。经氰胺处理后，血液乙醛含量增加。醋酸盐水平是恒定的，其轮廓几乎不受血液中乙醇水平的增加的影响。结果表明，乙醛和乙酸乙酯的动力学性质不同。

In Japan, there are many flushers who have flushing reactions during alcohol drinking, since they accumulate acetaldehyde due to partial defect of activity of aldehyde dehydrogeuase (ALDH2). We examined the effects of blood ethanol level on the disposition of acetaldehyde and acetate with and without cyanamide treatment, which is the inhibitor of ALDH2. Rabbits were used. An ethanol saline solution was administered intravenously into these rabbits at 1.0 or 2.0 g/kgBW for 20 minutes, followed by constant-rate infusion (0.25 g/kg/hr). At 4 and 8hr, the infusion rate was increased to 0.5 g/kg/hr for 1 hr. Blood ethanol, acetaldehyde and acetate concentrations were measured by headspace gas chromatography. We found that blood ethanol concentration reaches a steady state within 2 hours. The blood acetaldehyde concentration exhibited a spike-like increase in response to increases in the blood ethanol level, reaching a steady state around 1 hr after the increase. The change in concentration was in proportion to blood ethanol concentration, suggesting that acetaldehyde toxicity may increase with ethanol amount. We also found that blood acetate concentration reaches a steady state within 2 hr of administration. Blood acetaldehyde increased by the cyanamide treatment. The acetate level was constant, and its profile was hardly influenced by increases in the blood ethanol level. Our results indicate that the kinetic nature of acetaldehyde is different to that of acetate