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首页> 外文期刊>Archives of Toxicology >Age-related changes in hepatic expression and activity of cytochrome P450 in male rats
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Age-related changes in hepatic expression and activity of cytochrome P450 in male rats

机译：雄性大鼠肝脏表达和细胞色素P450活性的年龄相关变化

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摘要

Age-related changes in hepatic expression and activity of cytochrome P450 (CYP) were investigated in male rats aged 3 (weanling), 12 (young), 26 (adult), and 104 (old) weeks. Levels of microsomal protein, total CYP, and cytochrome b5 increased fully after puberty. CYP1A1 was detected only in 3-week-old rats, and CYP1A2, CYP2B1, and CYP2E1 were maximally expressed at 3 weeks but decreased at 12 and 26 weeks. CYP2C11 and CYP3A2 increased markedly after puberty and decreased with aging. Ethoxyresorufin-O-deethylase, methoxyresorufin-O-demethylase, pentoxyresorufin-O-depenthylase, and p-nitrophenol hydroxylase activities were at their highest in 3-week-old rats, and midazolam hydroxylase activity was at a maximum in 12-week-old rats but decreased with aging. The present results show that increasing age caused significant alterations in hepatic expression/activity of CYP isoforms in an isoform-specific manner. These results suggest that age-related changes in hepatic CYP isoforms may be an important factor for deciding the efficacy and safety of xenobiotics.
机译：在3周龄（断奶），12周龄（年轻），26周岁（成年）和104周岁（成年）的雄性大鼠中研究了肝脏表达和细胞色素P450（CYP）活性与年龄相关的变化。青春期后，微粒体蛋白，总CYP和细胞色素b 5 的水平完全升高。 CYP1A1仅在3周龄的大鼠中检测到，CYP1A2，CYP2B1和CYP2E1在3周时最大表达，而在12周和26周时降低。 CYP2C11和CYP3A2在青春期后显着增加，并随着衰老而降低。在3周龄的大鼠中，乙氧基间苯二酚-O-脱乙基酶，甲氧基间苯二酚-O-去甲基化酶，戊氧基间苯二酚-O-去甲基化酶和对硝基苯酚羟化酶活性最高，而咪达唑仑羟化酶活性在12周龄时最大。大鼠，但随着衰老而减少。目前的结果表明，随着年龄的增长，CYP亚型的肝脏表达/活性以亚型特异性的方式显着改变。这些结果表明，与年龄相关的肝CYP亚型变化可能是决定异源生物功效和安全性的重要因素。

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