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Tissue distribution and characterization of feline cytochrome P450 genes related to polychlorinated biphenyl exposure

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Title: Tissue distribution and characterization of feline cytochrome P450 genes related to polychlorinated biphenyl exposure
Authors: Khidkhan, Kraisiri Browse this author
Mizukawa, Hazuki Browse this author
Ikenaka, Yoshinori Browse this author
Nakayama, Shouta M. M. Browse this author
Nomiyama, Kei Browse this author
Yokoyama, Nozomu Browse this author
Ichii, Osamu Browse this author
Darwish, Wageh Sobhy Browse this author
Takiguchi, Mitsuyoshi Browse this author
Tanabe, Shinsuke Browse this author
Ishizuka, Mayumi Browse this author →KAKEN DB
Keywords: Cat
CYP
mRNA expression
PCBs
Metabolism
Issue Date: Dec-2019
Publisher: Elsevier
Journal Title: Comparative biochemistry and physiology Part C: Toxicology & pharmacology
Volume: 226
Start Page: UNSP 108613
Publisher DOI: 10.1016/j.cbpc.2019.108613
Abstract: Cats have been known to be extremely sensitive to chemical exposures. To understand these model species' sensitivity to chemicals and their toxicities, the expression profiles of xenobiotic-metabolizing enzymes should be studied. Unfortunately, the characterization of cytochrome P450 (CYP), the dominant enzyme in phase I metabolism, in eats has not extensively been studied. Polychlorinated biphenyls (PCBs) are known as CYP inducers in animals, but the information regarding the PCB-induced CYP expression in cats is limited. Therefore, in the present study, we aimed to elucidate the mRNA expression of the CYP1-CYP3 families in the cat tissues and to investigate the CYP mRNA expression related to PCB exposure. In cats, the greatest abundance of CYP1-CYP3 (CYP1A2, CYP2A13, CYP2C41, CYP2D6, CYP2E1, CYP2E2, CYP2F2, CYP2F5, CYP2J2, CYP2U1, and CYP3A132) was expressed in the liver, but some extrahepatic isozymes were found in the kidney (CYP1A1), heart (CYP1B1), lung (CYP2B11 and CYP2S1) and small intestine (CYP3A131). In cats, CYP1A1, CYP1A2 and CYP1B1 were significantly upregulated in the liver as well as in several tissues exposed to PCBs, indicating that these CYPs were distinctly induced by PCBs. The strong correlations between 3,3',4,4'-tetrachlorobiphenyl (CB77) and CYP1A1 and CYP1B1 mRNA expressions were noted, demonstrating that CB77 could be a potent CYP1 inducer. In addition, these CYP isoforms could play an essential role in the PCBs biotransformation, particularly 3-4 Cl-PCBs, because a high hydroxylated metabolite level of 3-4 Cl-OH-PCBs was observed in the liver.
Rights: © 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
http://creativecommons.org/licenses/by-nc-nd/4.0/
Type: article (author version)
URI: http://hdl.handle.net/2115/79882
Appears in Collections:獣医学院・獣医学研究院 (Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 石塚 真由美

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