Seitz H K, Xu Y, Simanowski U A, Osswald B
Department of Medicine, Salem Medical Center Heidelberg, Federal Republic of Germany.
Res Exp Med (Berl). 1992;192(3):205-12. doi: 10.1007/BF02576276.
It has been reported that aging strikingly decreases in vivo ethanol metabolism in F344 rats without major effects on hepatic alcohol dehydrogenase (ADH) activity. Because hepatic ADH activity is not always rate limiting in the oxidation of ethanol, we measured in vivo ethanol elimination rate (EER), hepatic ADH activity, and the hepatic-cytoplasmic and mitochondrial redox states after acute ethanol application in 2- and 12-month-old F344 rats of both sexes. In male, but not in female, animals EER decreased with age significantly, by 28% (P less than 0.01). The body-to-liver weight ratio was significantly increased in male (39.4 +/- 1.5 vs 46.5 +/- 2.0; P less than 0.05), but not in female, animals with age. Specific activity of ADH was not significantly changed by age, while the activity was significantly reduced with age in male, but not female, rats when related to body weight (5.1 +/- 0.4 vs 3.9 +/- 0.3 mumoles/100 g b.wt./min; P less than 0.05). The cytoplasmic, but not the mitochondrial (NAD+) to (NADH), ratio was significantly decreased with age in male livers (317 +/- 48 vs 793 +/- 128, P less than 0.05), while this was not the case in female livers. In summary, the data show a sex dependence of the effect of age on ethanol metabolism. The observed reduction in in vivo EER with age in male animals is due at least in part to an increased body-to-liver weight ratio, decreased hepatic ADH activity, and reduced availability of NAD+, the cofactor of the ADH reaction. The cause of this may be decreased transport of reducing equivalents through the mitochondrial membrane due to a lack of shuttle systems or a change in the physicochemical properties of the mitochondrial membrane, or decreased reutilization of NADH as NADPH resulting from a reduction of microsomal ethanol oxidation with age.
据报道，衰老显著降低了F344大鼠体内的乙醇代谢，而对肝脏乙醇脱氢酶（ADH）活性没有重大影响。由于肝脏ADH活性在乙醇氧化过程中并不总是限速的，我们测量了2月龄和12月龄的雌雄F344大鼠急性摄入乙醇后的体内乙醇消除率（EER）、肝脏ADH活性以及肝脏细胞质和线粒体的氧化还原状态。在雄性动物中，EER随年龄显著降低，降低了28%（P<0.01），而在雌性动物中则没有。随着年龄增长，雄性动物的体肝重量比显著增加（39.4±1.5对46.5±2.0；P<0.05），而雌性动物则没有。ADH的比活性没有因年龄而显著变化，但与体重相关时，雄性大鼠的活性随年龄显著降低，雌性大鼠则没有（5.1±0.4对3.9±0.3微摩尔/100克体重/分钟；P<0.05）。雄性肝脏中细胞质的（NAD+）与（NADH）比值随年龄显著降低（317±48对793±128，P<0.05），而线粒体的该比值没有变化，雌性肝脏中则不存在这种情况。总之，数据表明年龄对乙醇代谢的影响存在性别依赖性。在雄性动物中观察到的随着年龄增长体内EER降低至少部分是由于体肝重量比增加、肝脏ADH活性降低以及ADH反应的辅助因子NAD+的可用性降低。其原因可能是由于缺乏穿梭系统或线粒体膜物理化学性质的改变导致还原当量通过线粒体膜的转运减少，或者是由于随着年龄增长微粒体乙醇氧化减少导致NADH作为NADPH的再利用减少。
