Seitz H K, Meydani M, Ferschke I, Simanowski U A, Boesche J, Bogusz M, Hoepker W W, Blumberg J B, Russell R M
Department of Medicine, University of Heidelberg, Federal Republic of Germany.
Gastroenterology. 1989 Aug;97(2):446-56. doi: 10.1016/0016-5085(89)90082-6.
To investigate the effect of aging on ethanol metabolism, 24 male and female F344 rats aged 2 and 12 mo that were fed a laboratory diet received ethanol (1.2 and 2.5 g/kg body wt) intraperitoneally. In male rats, in vivo ethanol elimination significantly decreased according to age both at high (436 +/- 38 vs. 294 +/- 27 mg/kg.h; p less than 0.01) and low (365 +/- 19 vs. 261 +/- 8 mg/kg.h; p less than 0.01) blood ethanol concentrations. Age did not influence the specific activity of hepatic or gastric alcohol dehydrogenase, whereas the activity was significantly decreased with age in the liver (p less than 0.05) and in the stomach (p less than 0.001) when related to body weight. In addition, the activity of the hepatic microsomal ethanol oxidizing system decreased significantly according to age (8.7 +/- 0.5 vs. 6.00 +/- 0.3 nmol/min.mg micr. protein; p less than 0.001). To study the response of ethanol-metabolizing enzymes to chronic ethanol ingestion, 2- and 19-mo-old male F344 rats were pair-fed nutritionally adequate liquid diets containing 36% of total calories either as ethanol or isocaloric carbohydrate for 3 wk. In this experiment specific alcohol dehydrogenase activity was not significantly affected by age, whereas the hepatic microsomal function estimated by the determination of cytochrome P450, microsomal ethanol oxidizing system, and aniline hydroxylation as well as hepatic mitochondrial low Km-acetaldehyde dehydrogenase activity was found to be markedly depressed with age (p less than 0.01). Chronic ethanol consumption increased microsomal enzyme activities in older rats to levels comparable to those observed in young animals prior to ethanol administration. Chronic ethanol feeding also resulted in an increased hepatic fat accumulation, which was significantly enhanced in older rats. In contrast to male rats, in vivo ethanol metabolism was practically identical for 2- and 12-mo-old female rats. These data demonstrate an enhanced toxicity of alcohol in older compared to younger male but not female rats associated with a delay in alcohol elimination both at high and low ethanol blood concentrations and a decrease in ethanol- and acetaldehyde-metabolizing enzyme activities.
为研究衰老对乙醇代谢的影响，给24只2月龄和12月龄、喂食实验室饲料的雄性和雌性F344大鼠腹腔注射乙醇（1.2和2.5 g/kg体重）。在雄性大鼠中，无论高血乙醇浓度（436±38 vs. 294±27 mg/kg·h；p<0.01）还是低血乙醇浓度（365±19 vs. 261±8 mg/kg·h；p<0.01），体内乙醇清除率均随年龄显著降低。年龄对肝或胃乙醇脱氢酶的比活性无影响，然而，与体重相关时，肝脏（p<0.05）和胃（p<0.001）中该酶的活性随年龄显著降低。此外，肝微粒体乙醇氧化系统的活性随年龄显著降低（8.7±0.5 vs. 6.00±0.3 nmol/min·mg微粒体蛋白；p<0.001）。为研究乙醇代谢酶对慢性乙醇摄入的反应，将2月龄和19月龄雄性F344大鼠配对喂食营养充足的液体饲料，其中36%的总热量分别来自乙醇或等热量碳水化合物，持续3周。在该实验中，特异性乙醇脱氢酶活性未受年龄显著影响，而通过测定细胞色素P450、微粒体乙醇氧化系统、苯胺羟化以及肝线粒体低Km -乙醛脱氢酶活性评估的肝微粒体功能随年龄显著降低（p<0.01）。慢性乙醇摄入使老年大鼠微粒体酶活性增加至与乙醇给药前年轻动物相当的水平。慢性乙醇喂养还导致肝脏脂肪蓄积增加，老年大鼠中这种增加更为显著。与雄性大鼠不同，2月龄和12月龄雌性大鼠的体内乙醇代谢基本相同。这些数据表明，与年轻雄性大鼠相比，老年雄性大鼠对酒精的毒性增强，但雌性大鼠并非如此，这与高、低血乙醇浓度下酒精清除延迟以及乙醇和乙醛代谢酶活性降低有关。
