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首页> 外文期刊>Archives of Toxicology >Drug metabolizing enzyme expression in rat choroid plexus: effects of in vivo xenobiotics treatment
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Drug metabolizing enzyme expression in rat choroid plexus: effects of in vivo xenobiotics treatment

机译：大鼠脉络丛中药物代谢酶的表达：体内异种生物治疗的影响

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The presence of drug metabolizing enzymes in extrahepatic tissues such as the choroid plexus (CP) suggests that the CP, like the blood–brain barrier, affords a metabolic protection to the brain against xenobiotics. The CP, which is the principal site of formation of the cerebrospinal fluid (CSF), controls the exchange of many endogenous compounds and exogenous molecules between brain tissue and CSF. We present the changes in mRNA expression and enzymatic activities of UDP-glucuronosyltransferase, UGT1A6 isoform and NADPH-cytochrome P450 reductase, after in vitro treatment with xenobiotic molecules known to act in the liver as inducers or inhibitors of these drug metabolizing enzymes. Five study groups of male Sprague–Dawley rats were treated separately with 3-methylcholantrene (3-MC), phenobarbital (PB), dexamethasone (DEX), cyclosporine (CsA) or paraquat (PQ). Choroidal 1-naphthol glucuronidation activities were significantly induced by 3-MC and PQ administration (354 ± 85 and 257 ± 49 vs. 115 ± 24 nmol/h per mg protein, in control group), whereas the other molecules were without effect. Accordingly, UGT1A6 mRNA expression, measured by RT-PCR, was 2.3-fold higher after 3-MC treatment and 2.1-fold higher after PQ administration. By contrast, reductase activities and mRNA expression remained unchanged in the isolated choroids plexus in these experimental conditions. We present for the first time evidences that the choroids plexus express transcripts for both UGT1A6 and NADPH-cytochrome P450 reductase, and their mRNA expression can be differently regulated by exogenous factors. These results emphasize that xenobiotics could modulate the biotransformation of exogenous and/or endogenous compounds in the choroids plexus, and underline the role of UGTs in the maintenance of brain homeostasis.
机译：肝外组织（如脉络丛（CP））中存在药物代谢酶，这表明CP像血脑屏障一样，为大脑提供了针对异源生物的代谢保护。 CP是脑脊液（CSF）形成的主要部位，它控制着大脑组织和CSF之间许多内源性化合物和外源性分子的交换。我们介绍了在体外用已知在肝脏中充当这些药物代谢酶的诱导剂或抑制剂的异源生物分子处理后，UDP-葡萄糖醛酸糖基转移酶，UGT1A6亚型和NADPH-细胞色素P450还原酶的mRNA表达和酶活性的变化。五个Sprague-Dawley雄性大鼠研究组分别用3-甲基胆碱（3-MC），苯巴比妥（PB），地塞米松（DEX），环孢素（CsA）或百草枯（PQ）治疗。施用3-MC和PQ可显着诱导脉络膜1-萘酚葡萄糖醛酸化活性（对照组为354±85和257±49 vs. 115±24 nmol / h / mg蛋白，对照组），而其他分子则无作用。因此，通过RT-PCR测量的UGT1A6 mRNA表达在3-MC治疗后高2.3倍，在PQ给药后高2.1倍。相比之下，在这些实验条件下，分离的脉络丛中的还原酶活性和mRNA表达保持不变。我们首次提出证据，脉络丛表达UGT1A6和NADPH-细胞色素P450还原酶的转录本，它们的mRNA表达可能受到外源因子的不同调节。这些结果强调，异源生物可以调节脉络丛中外源性和/或内源性化合物的生物转化，并突显了UGT在维持脑稳态中的作用。

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