Ali B, Walford R L, Imamura T
Life Sci. 1985 Oct 14;37(15):1387-93. doi: 10.1016/0024-3205(85)90077-3.
Cytochrome P-450-dependent and independent metabolism of xenobiotics in the liver of C57BL/10ScSn male mice was investigated in relation to age and the age-related differences in response to treatment with polyriboinosinic-polyribocytidylic acid (poly IC), an interferon inducing agent. Young (3 months), middle-aged (15 months) and old (27 months) animals were studied. Mean survival time of males of this strain is 30-33 months. Age-related changes in the metabolism of xenobiotics included significant decreases between middle and old age in activities of the microsomal P-450-dependent mixed function oxidases (MFO), aryl hydrocarbon hydroxylase (AHH) and p-nitroanisole (p-NA) O-demethylase, but not 7-ethoxycoumarin (7-Ec) O-deethylase. Analysis of P-450-independent enzymes revealed a significant decrease in the epoxide hydrolase activity in the microsomes and cytosol from old compared to middle-aged or young mice. Glutathione S-transferase activity towards 1-chloro-2,4-dinitrobenzene (CDNB) was lower in cytosols of middle-aged and old than young mice. Carboxylesterase activity was not altered by age. Hepatic microsomal protein content was significantly higher in middle-aged and old than in young mice. Intraperitoneal treatment with a single dose of 5 mg/kg poly IC 24 hours before sacrifice resulted, for mice of all age groups, in a marked inhibition of activities of all 3 microsomal cytochrome P-450-dependent enzymes, without any changes in activities of the P-450-independent enzymes. The inhibition of AHH by poly IC was much higher in old and middle-aged than in young mice, averaging 87.1%, 74.5%, and 41.9%, respectively, in the 3 age groups. Poly IC treatment increased lipid peroxidation in liver homogenates of all groups of mice. Body and liver weights were not altered in animals of the 3 age groups by poly IC treatment, but hepatic microsomal protein contents were significantly decreased.
研究了C57BL/10ScSn雄性小鼠肝脏中细胞色素P - 450依赖性和非依赖性的外源性物质代谢与年龄的关系，以及对干扰素诱导剂聚肌苷酸 - 聚胞苷酸（poly IC）治疗反应的年龄相关差异。研究了年轻（3个月）、中年（15个月）和老年（27个月）的动物。该品系雄性动物的平均存活时间为30 - 33个月。外源性物质代谢的年龄相关变化包括中年和老年之间微粒体P - 450依赖性混合功能氧化酶（MFO）、芳烃羟化酶（AHH）和对硝基苯甲醚（p - NA）O - 脱甲基酶的活性显著降低，但7 - 乙氧基香豆素（7 - Ec）O - 脱乙基酶活性未降低。对P - 450非依赖性酶的分析显示，与中年或年轻小鼠相比，老年小鼠微粒体和细胞溶质中的环氧化物水解酶活性显著降低。中年和老年小鼠细胞溶质中对1 - 氯 - 2,4 - 二硝基苯（CDNB）的谷胱甘肽S - 转移酶活性低于年轻小鼠。羧酸酯酶活性不受年龄影响。中年和老年小鼠肝脏微粒体蛋白含量显著高于年轻小鼠。在处死前24小时腹腔注射单剂量5 mg/kg的poly IC，所有年龄组的小鼠均出现所有3种微粒体细胞色素P - 450依赖性酶活性的显著抑制，而P - 450非依赖性酶活性无任何变化。poly IC对AHH的抑制在老年和中年小鼠中比在年轻小鼠中高得多，3个年龄组的平均抑制率分别为87.1%、74.5%和41.9%。poly IC处理增加了所有组小鼠肝脏匀浆中的脂质过氧化。3个年龄组的动物经poly IC处理后体重和肝脏重量未改变，但肝脏微粒体蛋白含量显著降低。
