Effects of selected polychlorinated biphenyl (PCB) congeners on hepatic glutathione, glutathione-related enzymes, and selenium status: implications for oxidative stress
Effects of selected polychlorinated biphenyl (PCB) congeners on hepatic glutathione, glutathione-related enzymes, and selenium status: implications for oxidative stress
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DOI：
10.1016/s0006-2952(01)00668-2
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发表时间：
2001-08-01
影响因子：
5.8
通讯作者：
Robertson, LW
中科院分区：
文献类型：
--
作者：
Twaroski, TP;O'Brien, ML;Robertson, LW
多氯联苯（多氯联苯）诱导药物代谢，可导致多氯联苯本身的生物活化或可导致细胞内的氧化事件。本研究的目的是确定选择作为药物代谢底物或诱导剂的同源多氯联苯对肝脏谷胱甘肽、谷胱甘肽相关酶和硒状态的影响。雄性和雌性Sprague-Dawley大鼠每周注射两次1次pcpc3（4-氯苯）、pcpc28（2,4,4'-三氯联苯）、pcpc38（3,4,5-三氯联苯）、pcpc77（3,3',4,4',5,5'-四氯联苯）、pcpc153（2,2',4,4',5,5'-六氯联苯）或pcpc77和153 （100 μ mol/kg/注射），并在1、2或3周结束时杀死。制备全肝匀浆、肝细胞质和微粒体。在接受芳烃受体激动剂pcb77以及同时接受pcb77和pcb153的雄性和雌性大鼠中，谷胱甘肽还原酶和谷胱甘肽转移酶活性均显著增加。肝总谷胱甘肽水平无明显变化趋势。PCB 77处理显著降低了雄性和雌性大鼠肝脏硒依赖性谷胱甘肽过氧化物酶（SeGPX）活性。pc77处理后的活性降低伴随着胞质中硒依赖性谷胱甘肽过氧化物酶基因（GSPx1）转录物的减少，以及肝脏总硒水平的降低。这些数据支持这样一个概念，即暴露于共面PCB 77通过基因调控机制抑制细胞抗氧化酶SeGPX，这种减少与硒有关。低卤化多氯联苯可能对产生活性氧（ROS）的代谢物具有生物活性，而高卤化多氯联苯不是Ah受体激动剂，它们是无活性的。(C) 2001爱思唯尔科学公司版权所有。
Polychlorinated biphenyls (PCBs) induce drug metabolism that may lead to the bioactivation of PCBs themselves or alternatively may lead to oxidative events within the cell. The goal of the present study was to determine the influence of congeneric PCBs, selected as substrates for or inducers of drug metabolism, upon hepatic glutathione, glutathione-related enzymes, and selenium status. Male and female Sprague-Dawley rats received two i.p, injections per week of PCB 3 (4-chlorobiphenyl), PCB 28 (2,4,4'-trichlorobiphenyl), PCB 38 (3,4,5-trichlorobiphenyl), PCB 77 (3,3',4,4'-tetrachlorobiphenyl), PCB 153 (2,2',4,4',5,5'-hexachlorobiphenyl), or both PCBs 77 and 153 (100 mu mol/kg/injection) and were killed at the end of 1, 2, or 3 weeks. Whole liver homogenates, hepatic cytosol, and microsomes were prepared. Both glutathione reductase and glutathione transferase activities were increased significantly in both male and female rats receiving PCB 77, an aryl hydrocarbon receptor agonist, as well as in those receiving both PCBs 77 and 153. No significant trend was observed in the levels of hepatic total glutathione. PCB 77 treatment decreased hepatic selenium-dependent glutathione peroxidase (SeGPX) activity in both male and female rats significantly. This decrease in activity following PCB 77 treatment was accompanied by a decrease in the cytosolic selenium-dependent glutathione peroxidase gene (GSPx1) transcript, as well as a decrease in hepatic total selenium levels. These data support the concept that exposure to the coplanar PCB 77 suppresses, via gene regulatory mechanisms, the cellular antioxidant enzyme SeGPX and that this decrease involves selenium. Lower halogenated PCBs that may be bioactivated to reactive oxygen species (ROS)-producing metabolites, and higher halogenated PCBs that are not Ah receptor agonists, were inactive. (C) 2001 Elsevier Science Inc. All rights reserved.