Elliott C R, Prasad J S, Husby A D, Ellingson R J, Holtzman J L, Crankshaw D L
Alcohol. 1985 Jan-Feb;2(1):17-22. doi: 10.1016/0741-8329(85)90007-2.
Chronic alcohol consumption significantly increases the risk of drug interactions. We have described its effects on hamster microsomal monooxygenases. Male Syrian hamsters (85 g) were given 10% ethanol in water and food ad lib for up to 6 weeks. Microsomal electron transport components and metabolism of ethylmorphine, benzphetamine, aniline, and acetaminophen were measured. At 4 weeks, SDS-PAGE of ethanol microsomes showed an induced band with an Mr of 53,900 daltons and there was a 2-3 fold stimulation of aniline and acetaminophen metabolism. Cytochrome P-450 increase was not significant. For the six week period, Caloric intake (3 weeks, p less than 0.001), liquid consumption (3 weeks, p less than 0.05) and body weights (6 weeks, p less than 0.05) of ethanol animals were significantly greater than controls; kidney weights were significantly less (p less than 0.05). Ethanol consumption increased from 20% of the daily caloric intake (week 1) to 31% (week 6). Induction of specific substrate metabolism without apparent deleterious physiological changes establishes hamsters fed 10% ethanol in drinking water as a biochemical model for the study of chronic alcohol consumption and specific drug interactions.
长期饮酒会显著增加药物相互作用的风险。我们已经描述了其对仓鼠微粒体单加氧酶的影响。给雄性叙利亚仓鼠(85克)自由饮用含10%乙醇的水和食物,持续6周。测量微粒体电子传递成分以及乙基吗啡、苄非他明、苯胺和对乙酰氨基酚的代谢情况。4周时,乙醇处理组微粒体的SDS-PAGE显示出一条诱导带,其分子量为53,900道尔顿,苯胺和对乙酰氨基酚的代谢有2至3倍的刺激作用。细胞色素P-450的增加并不显著。在为期6周的时间里,乙醇处理组动物的热量摄入(3周,p<0.001)、液体摄入量(3周,p<0.05)和体重(6周,p<0.05)均显著高于对照组;肾脏重量则显著更低(p<0.05)。乙醇摄入量从每日热量摄入的20%(第1周)增加到31%(第6周)。在无明显有害生理变化的情况下诱导特定底物代谢,使得饮用含10%乙醇水的仓鼠成为研究长期饮酒和特定药物相互作用的生化模型。