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Comparison of warfarin sensitivity between rat and bird species

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Title: Comparison of warfarin sensitivity between rat and bird species
Authors: Watanabe, Kensuke P. Browse this author
Saengtienchai, Aksorn Browse this author
Tanaka, Kazuyuki D. Browse this author
Ikenaka, Yoshinori Browse this author →KAKEN DB
Ishizuka, Mayumi Browse this author →KAKEN DB
Keywords: Avian
Cytochrome P450 (CYP)
Inhibitor constant (Ki)
Vitamin K epoxide reductase (VKOR)
Vitamin K
Issue Date: Jun-2010
Publisher: Elsevier
Journal Title: Comparative Biochemistry and Physiology Part C : Toxicology & Pharmacology
Volume: 152
Issue: 1
Start Page: 114
End Page: 119
Publisher DOI: 10.1016/j.cbpc.2010.03.006
PMID: 20346414
Abstract: Scattering coumarin-derivative rodenticides in broad areas have caused primary- and secondary-poisoning incidents in non-target wild birds. In this study, we compared factors determining warfarin sensitivity between bird species and rats based on vitamin K 2,3-epoxide reductase (VKOR) kinetics, VKOR inhibition by warfarin and warfarin metabolism assays. In VKOR characterization, chickens and ostriches showed significantly lower enzymatic efficiencies than rats (one-sixth and one-third, respectively), suggesting bird species depend more on a non-VKOR vitamin K source. On the other hand, the inhibition constants (Ki) of VKOR for warfarin were significantly different between chickens and ostriches (113 ± 2.5 μM and 0.64 ± 0.39 μM, respectively). Interestingly, the ostrich Ki was similar to the values for rats (0.28 ± 0.09 μM). The Ki results reveal a surprising possibility that VKOR in some bird species are easily inhibited by warfarin. Warfarin metabolism assays also showed a large inter-species difference in bird species. Chickens and ostriches showed higher metabolic activity than that of rats, while mallards and owls showed only a slight ability to metabolize warfarin. In this study, we clarified the wide inter-species difference that exists among birds in xenobiotic metabolism and sensitivity to a rodenticide.
Type: article (author version)
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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