Strain differences in toxicity of vitamin K antagonist warfarin in rats

Abstract

Warfarin (4-hydroxy coumarin) is Vitamin K (VK) antagonist that inhibits Vitamin K-dependent (VKD) processes, such as blood coagulation. It exerts influence on some non-VKD-related activities as well. In this study, the effect of subacute (30-day) oral warfarin (2 mg L-1 and 1 mg L-1) intake on hematological parameters was examined in two rat strains, Albino Oxford (AO) and Dark Agouti (DA), that differ in their sensitivity to certain chemicals. Greater susceptibility to anticoagulant effect of 2 mg L-1 of warfarin was observed in AO rats and was associated with an increase in relevant hematological parameters in this strain. Although both strains responded to 2 mg L-1 of warfarin with quantitative changes in peripheral blood leukocytes differential bone marrow and lung responses were observed. Strain-related differences in proinflammatory activity of peripheral blood granulocytes and in mononuclear cell IFN-? production were observed. Recognition of differences in quantitative and qualitative effects of oral warfarin on processes other than hemostasis might be of relevance for those humans who are on warfarin therapy.