Tomita Y, Haseba T, Kurosu M, Watanabe T
Department of Legal Medicine, Nippon Medical School.
Arukoru Kenkyuto Yakubutsu Ison. 1990 Apr;25(2):116-28.
To elucidate the effects of acute ethanol intoxication on hepatic aldehyde dehydrogenase (ALDH), the activities of these isozymes were measured after acute ethanol injection at the doses of 1, 3 or 5 g/Kg body weight in mice. At the same time, blood ethanol and acetaldehyde levels were measured to consider their correlation to the changes in ALDH activities. In the cytosolic fraction, acute ethanol injection caused no effects on high Km ALDH. However, low Km ALDH activity decreased significantly after 0.5 and 12 hr at the dose of 5 g/Kg body weight. In the granule fraction, acute ethanol injection caused more than 50% loss of low Km ALDH activity after 2 to 8 hr at the dose of 1 g/Kg and after 0.5 to 8 hr at the dose of 3 or 5 g/Kg body weight, in comparison with the untreated group. However, high Km ALDH activity decreased only after 4 hr at the dose of 3 or 5 g/Kg body weight. The elimination rate of blood ethanol was 158.0 mumol/min/1 and 125.6 mumol/min/1 after 0.5 to 4 hr of ethanol injection at the dose of 3 or 5 g/Kg body weight, respectively. However, these elimination rates decreased drastically after 4 to 8 hr following ethanol injection. The elimination rate of blood acetaldehyde was 116.6 nmol/min/1 after 1 to 2 hr, and the rate decreased to 6.9 nmol/min/1 after 2 to 8 hr following ethanol injection at the dose of 5 g/Kg body weight. These drastic decreases in acetaldehyde elimination rate appear to be caused by reduction of the granule low Km ALDH activity.
为阐明急性乙醇中毒对肝脏醛脱氢酶(ALDH)的影响,在小鼠中以1、3或5 g/千克体重的剂量急性注射乙醇后,测量了这些同工酶的活性。同时,测量了血液中的乙醇和乙醛水平,以考虑它们与ALDH活性变化的相关性。在胞质部分,急性注射乙醇对高Km ALDH没有影响。然而,在5 g/千克体重的剂量下,0.5小时和12小时后,低Km ALDH活性显著降低。在颗粒部分,与未处理组相比,在1 g/千克体重的剂量下,2至8小时后,以及在3或5 g/千克体重的剂量下,0.5至8小时后,急性注射乙醇导致低Km ALDH活性损失超过50%。然而,仅在3或5 g/千克体重的剂量下,4小时后高Km ALDH活性才降低。在3或5 g/千克体重的剂量下,乙醇注射0.5至4小时后,血液乙醇的消除率分别为158.0 μmol/分钟/升和125.6 μmol/分钟/升。然而,乙醇注射后4至8小时,这些消除率急剧下降。在5 g/千克体重的剂量下,乙醇注射1至2小时后,血液乙醛的消除率为116.6 nmol/分钟/升,2至8小时后,该速率降至6.9 nmol/分钟/升。乙醛消除率的这些急剧下降似乎是由颗粒低Km ALDH活性的降低引起的。