ýý-Tocopherol injections in rats up-regulate hepatic ABC transporters, but not cytochrome P450 enzymes.
ýý-Tocopherol injections in rats up-regulate hepatic ABC transporters, but not cytochrome P450 enzymes.
复制标题
给大鼠注射 α-生育酚会上调肝脏 ABC 转运蛋白，但不会上调细胞色素 P450 酶。
DOI：
10.1016/j.freeradbiomed.2011.08.033
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发表时间：
2011
影响因子：
7.4
通讯作者：
Lebold,KatieM
中科院分区：
文献类型：
--
作者：
Traber,MaretG;Labut,EdwinM;Leonard,ScottW;Lebold,KatieM
过量服用维生素E时，肝脏外源性调节机制在调节肝脏α-生育酚浓度中的作用尚不清楚。我们假设肝脏α-生育酚的增加会引起明显的异种反应。因此，我们对大鼠每日注射α-生育酚（100mg/kg体重）长达9天后的细胞色素P450氧化系统（一期）、偶联系统（二期）和转运体（三期）进行了评估。注射α-生育酚可使肝脏α-生育酚浓度增加近20倍，肝脏α-生育酚代谢物α-CEHC和α-CMBHC增加10倍。α-生育酚注射对ⅰ期（CYP3A2、CYP3A1、CYP2B2）和ⅱ期（SULT2A1）蛋白和/或mrna的表达有不同程度的影响；而α-生育酚持续改变III期转运蛋白基因的表达。注射α-生育酚后，肝脏外排转运蛋白ABCB1b和ABCG2基因表达上调，而肝脏内流转运蛋白OATP基因表达下调。因此，肝脏α-生育酚超载会增加其自身的代谢，并增加转运蛋白基因的表达，这被认为会导致维生素E及其代谢物的排泄增加。
The role of hepatic xenobiotic regulatory mechanisms in modulating hepatic α-tocopherol concentrations during excess vitamin E administration remains unclear. We hypothesized that increased hepatic α-tocopherol would cause a marked xenobiotic response. Thus, we assessed cytochrome P450 oxidation systems (phase I), conjugation systems (phase II), and transporters (phase III) after daily α-tocopherol injections (100mg/kg body wt) for up to 9days in rats. α-Tocopherol injections increased hepatic α-tocopherol concentrations nearly 20-fold, along with a 10-fold increase in the hepatic α-tocopherol metabolites α-CEHC and α-CMBHC. Expression of phase I (CYP3A2, CYP3A1, CYP2B2) and phase II (SULT2A1) proteins and/or mRNAs was variably affected by α-tocopherol injections; however, expression of phase III transporter genes was consistently changed by α-tocopherol. Two liver efflux transporter genes, ABCB1b and ABCG2, were up-regulated after α-tocopherol injections, whereas OATP, a liver influx transporter, was down-regulated. Thus, an overload of hepatic α-tocopherol increases its own metabolism and increases expression of genes of transporters that are postulated to lead to increased excretion of both vitamin E and its metabolites.