Rikans L E
Department of Pharmacology, University of Oklahoma College of Medicine, Oklahoma City 73190.
Mech Ageing Dev. 1989 Jun;48(3):267-80. doi: 10.1016/0047-6374(89)90088-2.
The purpose of this study was to determine how aging affects the induction by ethanol or acetone of the hepatic microsomal monooxygenase system of female Fischer 344 rats. Young-adult, middle-aged and old rats (4, 14 and 25 months) were fed an ethanol-containing or control liquid diet for 15 days. Cytochrome P-450, cytochrome c reductase, aniline hydroxylase, nitrophenol hydroxylase, nitroanisole O-demethylase and benzphetamine N-demethylase activities were measured in hepatic microsomes. All of the drug metabolism activities except benzphetamine N-demethylase were 20-35% lower in old than in young-adult rats fed the control diet. In addition, the increase in drug metabolism produced by feeding the regular ethanol diet (36% of calories as ethanol) was 50-60% lower in the old rats. However, there was no difference in the magnitude of ethanol induction when ethanol intakes were matched. The effects of chronic acetone consumption (1.2g/day per kg body weight for 15 days) paralleled those of ethanol consumption, except that the extent of induction was greater with acetone. Acetone-induced levels of hepatic microsomal cytochrome P-450, nitrophenol hydroxylase, nitroanisole O-demethylase and aniline hydroxylase were similar in all three age groups. The results of this study indicate that induction of hepatic microsomal drug metabolism by ethanol or acetone is unaffected by the aging process.
本研究的目的是确定衰老如何影响雌性Fischer 344大鼠肝脏微粒体单加氧酶系统由乙醇或丙酮诱导的情况。将年轻成年、中年和老年大鼠（4、14和25个月）喂食含乙醇或对照液体饮食15天。测定肝脏微粒体中的细胞色素P-450、细胞色素c还原酶、苯胺羟化酶、硝基苯酚羟化酶、硝基苯甲醚O-脱甲基酶和苄非他明N-脱甲基酶活性。除苄非他明N-脱甲基酶外，所有药物代谢活性在喂食对照饮食的老年大鼠中比年轻成年大鼠低20-35%。此外，喂食常规乙醇饮食（乙醇占卡路里的36%）所产生的药物代谢增加在老年大鼠中低50-60%。然而，当乙醇摄入量相匹配时，乙醇诱导的程度没有差异。慢性丙酮消耗（15天内每千克体重每天1.2克）的影响与乙醇消耗相似，只是丙酮诱导的程度更大。在所有三个年龄组中，丙酮诱导的肝脏微粒体细胞色素P-450、硝基苯酚羟化酶、硝基苯甲醚O-脱甲基酶和苯胺羟化酶水平相似。本研究结果表明，乙醇或丙酮对肝脏微粒体药物代谢的诱导不受衰老过程的影响。
