Salaspuro M P, Pikkarainen P, Lindros K
Eur J Clin Invest. 1977 Dec;7(6):487-90. doi: 10.1111/j.1365-2362.1977.tb01640.x.
Infusion of ethanol (0.6 g/kg body wt) caused marked hypoglycaemia in subjects fasted for 36 h. Previous administration of the alcohol dehydrogenase (ADH) inhibitor 4-methylpyrazole (4-MP, 7 mg/kg body wt i.v.) strongly suppressed the ethanol-induced hypoglycaemia. The rate of ethanol elimination was 84.6 mg/kg per hour. 4-MP at the dose used caused a 21% reduction of ethanol elimination, but had no significant effect on blood acetaldehyde levels. 4-MP also significantly suppressed the ethanol-induced elevation of blood lactate and almost completely prevented the increase in the 3-hydroxybutyrate/acetoacetate ratio, but had only a slight effect on the lactate/pyruvate ratio of venous blood. The results demonstrate that the hypoglycaemia and lactacidaemia produced by the oxidation of alcohol can be prevented by a dose of 4-MP that diminishes or prevents the ethanol-induced shift in the NAD-coupled redox state of the liver.
给禁食36小时的受试者输注乙醇(0.6克/千克体重)会导致明显的低血糖。预先静脉注射乙醇脱氢酶(ADH)抑制剂4-甲基吡唑(4-MP,7毫克/千克体重)可强烈抑制乙醇诱导的低血糖。乙醇的消除速率为每小时84.6毫克/千克。所用剂量的4-MP使乙醇消除率降低了21%,但对血液乙醛水平无显著影响。4-MP还显著抑制了乙醇诱导的血液乳酸升高,并几乎完全阻止了3-羟基丁酸/乙酰乙酸比值的增加,但对静脉血乳酸/丙酮酸比值只有轻微影响。结果表明,通过一定剂量的4-MP可预防由酒精氧化产生的低血糖和乳酸性血症,该剂量可减少或防止乙醇诱导的肝脏NAD偶联氧化还原状态的改变。