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首页> 外文期刊>Journal of biochemical and molecular toxicology >Effects of age and pregnancy on cytochrome P450 induction by octamethyltetracyclosiloxane in female Sprague-Dawley rats.
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Effects of age and pregnancy on cytochrome P450 induction by octamethyltetracyclosiloxane in female Sprague-Dawley rats.

机译：年龄和妊娠对雌性Sprague-Dawley大鼠中八甲基四环硅氧烷诱导细胞色素P450的影响。

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摘要

Dimethylcyclosiloxanes (DMCS) are components of silicone gel containing implants and are known inducers of human drug metabolizing enzymes. The effects of the major DMCS, octamethyltetracyclosiloxane (D4) on cytochrome P450 (CYP) induction were examined in young adult, mature, and pregnant female Sprague-Dawley rats. Also, the ability of D4 administered to pregnant dams to affect CYP expression in fetal liver was examined. Female young, mature, and pregnant Sprague-Dawley rats were administered 0, 5, 20, and 100 mg/kg D4 daily by gavage for 8 days. Liver microsomal CYP (CYP2B, CYP3A, CYP1A) concentrations were evaluated by Western blots using specific antisera, and CYP activities were assayed using CYP selective assays. D4 treatment resulted in a significant induction of CYP2B and CYP3A isoforms. CYP induction was dose and age dependent. A comparison of the inducibility of CYP3A protein by D4 in rats from different age groups showed that the degree of increase was the highest in the pregnant rats at doses of 20 mg/kg D4 or higher. The mature rats had a lesser degree of responsiveness than did the young rats at the dose of 100 mg/ kg D4. Significant increases in CYP2B immunoreactive protein concentrations were observed in young and mature rats given D4 at doses >5 mg/kg and in pregnant rats at doses >20 mg/kg. Maximal CYP2B induction detected with blotting was more than 90-fold in mature rats; however, no significant changes were detected in CYP1A expression. There was a 20% increase of liver to body weight ratio in the mature rats treated with 100 mg/kg D4. D4 has different inductive properties in female rats of different ages and reproductive status. Also, D4 administered to the pregnant dam is capable of inducing CYP expression in fetal liver as well as decreasing fetal body weight. (c) 2005 Wiley Periodicals, Inc. J Biochem Mol Toxicol 19:129-138, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20059.
机译：二甲基环硅氧烷（DMCS）是含有硅凝胶的植入物的成分，是已知的人类药物代谢酶的诱导剂。在成年，成年和怀孕的雌性Sprague-Dawley大鼠中检查了主要的DMCS八甲基四环硅氧烷（D4）对细胞色素P450（CYP）诱导的影响。另外，还检查了给予孕妇水坝的D4影响胎儿肝脏中CYP表达的能力。每天通过管饲法向雌性，成年和怀孕的Sprague-Dawley雌鼠每天分别给药0、5、20和100 mg / kg D4，持续8天。使用特异性抗血清通过Western印迹法评估肝脏微粒体CYP（CYP2B，CYP3A，CYP1A）的浓度，并使用CYP选择性测定法测定CYP活性。 D4处理导致CYP2B和CYP3A亚型的显着诱导。 CYP诱导与剂量和年龄有关。 D4对不同年龄组大鼠的CYP3A蛋白诱导能力的比较表明，剂量在20 mg / kg D4或更高剂量的情况下，孕鼠的增加程度最高。在剂量为100 mg / kg D4的情况下，成年大鼠的反应程度比年轻大鼠低。在剂量大于5 mg / kg的D4幼鼠和成年大鼠中，以及剂量大于20 mg / kg的怀胎大鼠中，CYP2B免疫反应蛋白浓度均显着增加。在成熟大鼠中，通过印迹检测到的最大CYP2B诱导率是90倍以上;然而，没有检测到CYP1A表达的显着变化。用100 mg / kg D4处理的成熟大鼠的肝脏与体重之比增加了20％。 D4在不同年龄和生殖状态的雌性大鼠中具有不同的诱导特性。同样，给予妊娠大坝的D4能够诱导胎儿肝脏中的CYP表达并降低胎儿体重。 （c）2005 Wiley Periodicals，Inc. J Biochem Mol Toxicol 19：129-138，2005;在线发布于Wiley InterScience（www.interscience.wiley.com）。 DOI 10.1002 / jbt.20059。

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