Distribution and excretion of 2,2′,3,4′,5,5′,6-heptachlorobiphenyl (CB187) and its metabolites in rats and guinea pigs
Distribution and excretion of 2,2′,3,4′,5,5′,6-heptachlorobiphenyl (CB187) and its metabolites in rats and guinea pigs
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DOI：
10.1016/j.chemosphere.2014.05.019
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发表时间：
2015-01-01
期刊：
影响因子：
8.8
通讯作者：
Koga, Nobuyuki
中科院分区：
文献类型：
--
作者：
Ohta, Chiho;Haraguchi, Koichi;Koga, Nobuyuki
4-羟基（OH）-2，2 '，3，4'，5，5 '，6-七氯联苯（CB 187）是一种多氯联苯（PCB）代谢物，在人体血清中的浓度最高。我们的前期研究表明，CB 187在大鼠和豚鼠肝微粒体中代谢为主要代谢产物4 '-OH-2，2'，3，3 '，5，5'，6-七氯联苯（CB 178）和两种次要代谢产物4-OH-CB 187和4 '-OH-2，2'，3，5，5 '，6-六氯联苯（CB 151）。在本研究中，在腹腔内给予CB 187的大鼠和豚鼠中检查了这些代谢物在血清、肝脏和肾脏中的分布及其粪便排泄。与体外研究相似，在注射CB 187后第4天，4 '-OH-CB 178是两种动物种属肝脏、血清和粪便中的主要代谢产物，未给药豚鼠中肝脏中的水平比未给药大鼠高约20倍。此外，在豚鼠和大鼠的血清和肾脏中检测到少量代谢产物4-OH-CB 187，但在粪便中未检测到。另一种次要代谢产物4 '-OH-CB 151仅在豚鼠粪便中检测到较低水平;在两种动物的血清或肝脏中均几乎未发现。豚鼠注射CB 187后30 d内，血清中4 '-OH-CB 178和4-OH-CB 187分别在注射后第4天和第16天达到较高水平。大部分的4 '-OH-CB 178在未被代谢的CB 187后被迅速排泄到粪便中，而在30 d内未在豚鼠粪便和肝脏中发现4-OH-CB 187。这些结果支持先前的报告，即4-OH-CB 187在动物血液中持续保留。(C)2014爱思唯尔有限公司版权所有。
4-Hydroxy (OH)-2,2',3,4',5,5',6-heptachlorobiphenyl (CB187) is a polychlorinated biphenyl (PCB) metabolite present in human serum at the highest concentration of the PCB metabolites. Our previous study demonstrated that CB187 was metabolized by rat and guinea pig liver microsomes to the major metabolite 4'-OH-2,2',3,3',5,5',6-heptachlorobiphenyl (CB178), and the two minor metabolites 4-OH-CB187 and 4'-OH-2,2',3,5,5',6-hexachlorobiphenyl (CB151). In this study, the distribution of these metabolites in serum, liver and kidney, and their fecal excretion, were examined in rats and guinea pigs intraperitoneally dosed with CB187. Similarly to the in vitro study, 4'-OH-CB178 was a major metabolite in the liver, serum and feces of both animal species on day 4 after CB187 injection, and the level in the liver was about 20 times higher in untreated guinea pigs than in untreated rats. In addition, 4-OH-CB187, a minor metabolite, was detected in the serum and kidneys, but not in the feces, of both guinea pigs and rats. Another minor metabolite, 4'-OH-CB151, was detected at a lower level only in guinea pig feces; little was found in the serum or liver of either animals. Over the 30 d following CB187 injection into guinea pigs, 4'-OH-CB178 and 4-OH-CB187 in the serum was observed at higher level on day 4 and day 16 after injection, respectively. The majority of the 4'-OH-CB178 was rapidly excreted to the feces following unmetabolized CB187, whereas 4-OH-CB187 was not found in guinea pig feces and liver during 30 d. These results support previous reports that 4-OH-CB187 is retained persistently in animal blood. (C) 2014 Elsevier Ltd. All rights reserved.