Vitamin K antagonism of coumarin intoxication in the rat

R. Wallin, S. D. Patrick, James Ballard

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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 K1 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 K1 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.

Original languageEnglish (US)
Pages (from-to)235-239
Number of pages5
JournalThrombosis and Haemostasis
Volume55
Issue number2
StatePublished - Jan 1 1986

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Vitamin K
Dicumarol
Vitamin K 1
Blood Coagulation Factors
Liver
Warfarin
Vitamin K Epoxide Reductases
Blood Coagulation
Liver Microsomes
Enzymes
coumarin
In Vitro Techniques
difenacoum

All Science Journal Classification (ASJC) codes

  • Hematology

Cite this

Wallin, R. ; Patrick, S. D. ; Ballard, James. / Vitamin K antagonism of coumarin intoxication in the rat. In: Thrombosis and Haemostasis. 1986 ; Vol. 55, No. 2. pp. 235-239.
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Vitamin K antagonism of coumarin intoxication in the rat. / Wallin, R.; Patrick, S. D.; Ballard, James.

In: Thrombosis and Haemostasis, Vol. 55, No. 2, 01.01.1986, p. 235-239.

Research output: Contribution to journalArticle

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