Ohta Chiho, Haraguchi Koichi, Kato Yoshihisa, Endo Tetsuya, Kimura Osamu, Koga Nobuyuki
Faculty of Nutritional Sciences, Nakamura Gakuen University, 5-7-1 Befu, Jonan-ku, Fukuoka 814-0198, Japan.
Daiichi College of Pharmaceutical Sciences, 22-1 Tamagawa-cho, Minami-ku, Fukuoka 815-8511, Japan.
Chemosphere. 2015 Jan;118:5-11. doi: 10.1016/j.chemosphere.2014.05.019. Epub 2014 Jun 13.
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 30d 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 30d. These results support previous reports that 4-OH-CB187 is retained persistently in animal blood.
4-羟基（OH）-2,2',3,4',5,5',6-七氯联苯（CB187）是一种多氯联苯（PCB）代谢物，在人体血清中的浓度是PCB代谢物中最高的。我们之前的研究表明，CB187被大鼠和豚鼠肝微粒体代谢为主要代谢物4'-OH-2,2',3,3',5,5',6-七氯联苯（CB178），以及两种次要代谢物4-OH-CB187和4'-OH-2,2',3,5,5',6-六氯联苯（CB151）。在本研究中，对腹腔注射CB187的大鼠和豚鼠体内这些代谢物在血清、肝脏和肾脏中的分布及其粪便排泄情况进行了检测。与体外研究相似，在注射CB187后第4天，4'-OH-CB178是两种动物肝脏、血清和粪便中的主要代谢物，未处理的豚鼠肝脏中的水平比未处理的大鼠高约20倍。此外，次要代谢物4-OH-CB187在豚鼠和大鼠的血清及肾脏中均有检测到，但在粪便中未检测到。另一种次要代谢物4'-OH-CB151仅在豚鼠粪便中以较低水平检测到；在两种动物的血清或肝脏中均未发现。在向豚鼠注射CB187后的30天内，血清中的4'-OH-CB178和4-OH-CB187分别在注射后第4天和第16天观察到较高水平。大部分4'-OH-CB178在未代谢的CB187之后迅速排泄到粪便中，而在30天内豚鼠粪便和肝脏中均未发现有4-OH-CB187。这些结果支持了之前的报道，即4-OH-CB187在动物血液中持续留存。
