Birt D F, Hruza D S, Baker P Y
Drug Nutr Interact. 1984;3(1):1-10.
The influence of age on hepatic microsomal drug metabolism was determined in male and female Syrian hamsters fed purified diet or commercial ration. Data from hamsters are reported on hepatic contents of microsomal protein and cytochrome P450, as well as activities of arylhydrocarbon hydroxylase and aniline hydroxylase measured at 4, 10, 22, 34, and 64 weeks of age. Hepatic microsomal protein increased at 34 and 64 weeks in hamsters fed purified diet and at 64 weeks in those fed commercial diet. Cytochrome P450 liver content, based on microsomal protein, was highest at 10 weeks in hamsters given purified diets. Peak values were less with the commercial diet and did not differ between 10, 22, and 34 weeks. When expressed on a body weight basis, cytochrome P450 values increased between 4 and 10 weeks in all groups, except in males fed purified diet, in which values increased up to 34 weeks. Arylhydrocarbon hydroxylase activity increased between 4 and 10, 22 or 34 weeks and declined by 64 weeks in every group when based on microsomal protein content or body weight. Aniline hydroxylase activity, based on microsomal protein, increased between 4 and 10 or 22 weeks and then declined by 64 weeks in every group, except in females fed commercial diet, in which no increase occurred. Changes in aniline hydroxylase, based on body weight, were not consistent with these patterns. Maximum values occurred at 4 weeks for females and at 22 weeks for males fed purified diet, but at 10 weeks in males given commercial diet. Declines in drug metabolism between maturity and senescence were greater when data were expressed on the basis of microsomal protein content, when compared with data on a body weight basis.
在喂食纯化饲料或商业日粮的雄性和雌性叙利亚仓鼠中，测定了年龄对肝脏微粒体药物代谢的影响。报告了仓鼠在4、10、22、34和64周龄时，肝脏微粒体蛋白和细胞色素P450的含量，以及芳烃羟化酶和苯胺羟化酶的活性。喂食纯化饲料的仓鼠在34周和64周时肝脏微粒体蛋白增加，喂食商业日粮的仓鼠在64周时肝脏微粒体蛋白增加。以微粒体蛋白为基础，喂食纯化饲料的仓鼠肝脏细胞色素P450含量在10周时最高。商业日粮组的峰值较低，在10、22和34周之间没有差异。以体重为基础计算时，除喂食纯化饲料的雄性仓鼠外，所有组的细胞色素P450值在4至10周之间增加，而喂食纯化饲料的雄性仓鼠的值在34周之前一直增加。基于微粒体蛋白含量或体重，芳烃羟化酶活性在4至10、22或34周之间增加，在64周时每组均下降。基于微粒体蛋白，苯胺羟化酶活性在4至10或22周之间增加，然后在64周时每组均下降，但喂食商业日粮的雌性仓鼠除外，其苯胺羟化酶活性没有增加。以体重为基础计算时，苯胺羟化酶的变化与这些模式不一致。喂食纯化饲料的雌性仓鼠在4周时达到最大值，雄性在22周时达到最大值，但喂食商业日粮的雄性仓鼠在10周时达到最大值。与以体重为基础的数据相比，当以微粒体蛋白含量为基础表示数据时，成熟和衰老之间药物代谢的下降幅度更大。
