Vitamin K Antagonism of Coumarin Intoxication in the Rat
Vitamin K Antagonism of Coumarin Intoxication in the Rat
复制标题
维生素 K 拮抗大鼠香豆素中毒
DOI：
--
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发表时间：
1986
影响因子：
6.7
通讯作者：
J. Ballard
中科院分区：
文献类型：
--
作者：
R. Wallin;D. Susan;D. Patrick;J. Ballard
本文从华法林、苯那普隆和双酚A分别过量给药的大鼠肝脏中制备了一种表达与维生素K依赖的凝血因子羧化有关的所有酶活性的体外系统。在该体系中，测量了两条已知的产生活性还原维生素K1辅因子的羧化反应途径的活性。此外，还研究了高浓度维生素Kx克服凝血因子合成抑制的能力。在华法林和苯那普胺中毒大鼠的肝脏制备的系统中，途径I是不活跃的。维生素K环氧化物还原酶也没有活性，这强烈表明该酶在体内催化途径I的活性。途径II的维生素还原绕过了不活跃的途径I，导致了羧化活性。因此，这一途径介导了维生素K1在香豆素中毒肝脏中的解毒作用。在双库马罗尔中毒的肝脏制备的体外系统中，途径I的活性没有受到明显影响。然而，当在体外将地库马洛尔添加到肝微粒体中时，它是一种很强的抑制剂。
Summary An in vitro system which expresses all enzyme activities related to vitamin K-dependent carboxylation of blood clotting factors was prepared from livers of rats overdosed with warfarin, difenacoum and dicumarol respectively. In this system, the activities of the two pathways that are known to produce active reduced vitamin K1 cofactor for the carboxylation reaction were measured. Also the ability of high concentrations of vitamin Kx to overcome inhibition of clotting factor synthesis was studied. In the systems prepared from livers of warfarin and difenacoum intoxicated rats, pathway I was inactive. Vitamin K epoxide reductase was also inactive which strongly suggests that this enzyme catalyzes the activity of pathway I in vivo. Reduction of vitamin by pathway II bypassed the inactive pathway I and resulted in carboxylation activity. This pathway therefore mediates the antidotic effect of vitamin K1 in the coumarin intoxicated liver. In the in vitro system prepared from dicumarol intoxicated livers the activity of pathway I was not significantly affected. Dicumarol however was a strong inhibitor when added to liver microsomes in vitro.
肝脏中维生素 K 依赖性羧化和维生素 K 代谢。
DOI：
10.1172/jci112182
发表时间：
1985
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Wallin,R;Martin,LF
通讯作者：
Martin,LF
香豆素作用机制：正常和华法林耐药大鼠肝脏维生素 K 代谢酶的敏感性。
影响因子：
2.9
作者：
Hildebrandt,EF;Suttie,JW
通讯作者：
Suttie,JW