Department of Histology, Medical University of Silesia, ul. Medyków 18, 40-752, Katowice, Poland,
Genes Nutr. 2012 Apr;7(2):197-207. doi: 10.1007/s12263-011-0240-z. Epub 2011 Jul 17.
It has been established beyond doubt that, as well as the liver, the small intestine is an important site of first-pass metabolism of numerous drugs, food components and toxic xenobiotics. However, there is not much information available about age-dependent changes of intestinal biotransformation pathways. In the present paper, we evaluated the relationships between intestinal cytochrome P450 complex activity and the age of animals. The study was carried out on male Sprague-Dawley rats (n = 5) from 5 age series: 0.5-, 2-, 4-, 20-, and 28 months old. Animals at every age series were divided into 4 groups: control and three groups of rats treated with the CYP450 specific inducers: phenobarbital, β-naphtoflavone and dexamethasone, respectively. RNA was isolated from intestinal mucosa, and then standard RT-PCR was used for the analysis of CYP1A1, CYP2B1/2 and CYP3A1 mRNA expression. Additionally, the activities of NADPH-cytochrome P450 and NADH-cytochrome b(5) reductases in the microsomal fraction were biochemically estimated. The constitutive intestinal CYP1A1 mRNA expression changes during maturation and aging. Inducibility of CYP1A1 gene was evident in intestinal mucosa at 2-, 4- and 20-month-old rats. A similar pattern of changes was observed for CYP2B1/2 isoforms. CYP3A1 mRNA expression was not detected in small intestine of 2-week-old rats. In matured rats, constitutive intestinal CYP3A1 expression was low, although after induction, significant increases in CYP3A1 mRNA amount were noted in aged individuals. Intestinal activity of both analyzed reductases was lowest in immature rats and highest in 28-month-old animals. In conclusion, the activity of cytochrome P450 complex in rat small intestine was not decreased by the aging processes, so the high rate of oxidative metabolic reactions in intestinal mucosa can be maintained till the advanced life stage.
毫无疑问，除了肝脏，小肠也是许多药物、食物成分和有毒外来化合物首过代谢的重要部位。然而，关于肠道生物转化途径随年龄变化的信息并不多。在本文中，我们评估了肠道细胞色素 P450 复合酶活性与动物年龄之间的关系。该研究在 5 个年龄系列的雄性 Sprague-Dawley 大鼠（n=5）上进行：0.5、2、4、20 和 28 个月大。每个年龄系列的动物分为 4 组：对照组和 3 组分别用 CYP450 特异性诱导剂苯巴比妥、β-萘黄酮和地塞米松处理的大鼠。从肠黏膜中分离 RNA，然后使用标准 RT-PCR 分析 CYP1A1、CYP2B1/2 和 CYP3A1 mRNA 的表达。此外，还通过生化方法测定微粒体部分中 NADPH-细胞色素 P450 和 NADH-细胞色素 b(5)还原酶的活性。在成熟和老化过程中，肠道 CYP1A1 mRNA 的组成型表达发生变化。在 2、4 和 20 月龄大鼠的肠道黏膜中，CYP1A1 基因的诱导作用明显。CYP2B1/2 同工型也观察到类似的变化模式。在 2 周龄大鼠的小肠中未检测到 CYP3A1 mRNA 的表达。在成熟大鼠中，肠道 CYP3A1 的组成型表达水平较低，但在诱导后，老年个体的 CYP3A1 mRNA 量显著增加。两种分析还原酶的肠道活性在未成熟大鼠中最低，在 28 月龄动物中最高。总之，大鼠小肠细胞色素 P450 复合酶的活性并未因衰老过程而降低，因此肠道黏膜中的高氧化代谢反应速率可维持到老年阶段。
