Comparison of warfarin sensitivity between rat and bird species
Comparison of warfarin sensitivity between rat and bird species
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DOI：
10.1016/j.cbpc.2010.03.006
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发表时间：
2010-06-01
影响因子：
3.9
通讯作者：
Ishizuka, Mayumi
中科院分区：
文献类型：
--
作者：
Watanabe, Kensuke P.;Saengtienchai, Aksorn;Ishizuka, Mayumi
大面积散放香豆素类杀鼠剂已造成非靶向野鸟的原发性和继发性中毒事件。在这项研究中，我们比较了因素决定华法林敏感性鸟类和大鼠之间的基础上维生素K 2，3-环氧化物还原酶（VKOR）动力学，VKOR抑制华法林和华法林代谢测定。在VKOR表征中，鸡和鸵鸟的酶效率显着低于大鼠（分别为六分之一和三分之一），这表明鸟类更依赖于非VKOR维生素K来源。另一方面，VKOR对华法林的抑制常数（Ki）在鸡和鸵鸟之间存在显著差异（分别为113 +/- 2.5 μ M和0.64 +/- 0.39 μ M）。有趣的是，鸵鸟K-i与大鼠的值相似（0.28 +/- 0.09 μ M）。K-i结果揭示了一种令人惊讶的可能性，即华法林很容易抑制某些鸟类的VKOR。Warcantine代谢测定也显示了鸟类物种间的巨大差异。鸡和鸵鸟表现出比大鼠更高的代谢活性，而野鸭和猫头鹰只表现出轻微的代谢华法林的能力。在这项研究中，我们澄清了广泛的物种间的差异，存在于鸟类之间的外源性物质代谢和敏感性的灭鼠剂。(C)2010年爱思唯尔公司All rights reserved.
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 (K-i) of VKOR for warfarin were significantly different between chickens and ostriches (113 +/- 2.5 mu M and 0.64 +/- 0.39 mu M, respectively). Interestingly, the ostrich K-i was similar to the values for rats (0.28 +/- 0.09 mu M). The K-i 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. (C) 2010 Elsevier Inc. All rights reserved.