Loomis C W, Brien J F
Can J Physiol Pharmacol. 1984 May;62(5):544-50. doi: 10.1139/y84-087.
Ethanol (0.3 g/kg) was administered intravenously to adult, male rats at 3 h or at 1 and 3 h after gastric intubation of 7 mg/kg calcium carbimide (CC). For animals administered CC and two ethanol doses, blood ethanol concentration was similar for the two doses; however, blood acetaldehyde concentration was significantly less for the second ethanol dose compared with the first dose as determined by the area-under-curve data. Hepatic aldehyde dehydrogenase activity was determined over the 3.5- to 5-h interval after CC pretreatment. The inhibition of low Km and high Km aldehyde dehydrogenase activity in liver homogenate and in hepatic mitochondrial, cytosolic, and microsomal fractions was significantly less for rats administered CC followed by two ethanol doses compared with that for animals administered CC alone or CC followed by one ethanol dose. The data demonstrate that increased acetaldehyde concentration, produced during the CC - ethanol interaction, can augment the recovery of hepatic aldehyde dehydrogenase activity following CC pretreatment and indicate the existence of a displaceable enzyme inhibitor derived from CC.
给成年雄性大鼠静脉注射乙醇(0.3 g/kg),注射时间分别为胃内插管给予7 mg/kg卡巴咪嗪(CC)后3小时,或1小时和3小时。对于给予CC和两剂乙醇的动物,两剂乙醇的血乙醇浓度相似;然而,根据曲线下面积数据确定,第二剂乙醇的血乙醛浓度与第一剂相比显著降低。在CC预处理后的3.5至5小时内测定肝醛脱氢酶活性。与单独给予CC或给予CC后再给予一剂乙醇的动物相比,给予CC后再给予两剂乙醇的大鼠,其肝匀浆以及肝线粒体、胞质和微粒体部分中低Km和高Km醛脱氢酶活性的抑制作用明显较小。数据表明,CC与乙醇相互作用过程中产生的乙醛浓度升高,可增强CC预处理后肝醛脱氢酶活性的恢复,并表明存在一种源自CC的可置换酶抑制剂。