title: Effects of subacute oral warfarin administration on peripheral blood granulocytes in rats.
abstract: Warfarin affects mainly vitamin K dependent (VKD) processes, but the effects on some non-VKD-related activities such as tumor growth inhibition and mononuclear cell-mediated immune reactions were shown as well. In this study, the effect of subchronic (30 days) oral warfarin (0.35 mg/l and 3.5mg/l) intake on peripheral blood granulocytes in rats was investigated. Increase in prothrombin and partial thromboplastin time at high warfarin dose reflected its basic activity. Priming effect for respiratory burst was noted at both warfarin doses, while only high warfarin dose resulted in priming for adhesion, the rise in intracellular myeloperoxidase content/release and stimulation of nitric oxide production. Differential effects of high warfarin dose were noted on granulocyte cytokines IL-6 (lack of the effect), TNF-α (decreased release and mRNA expression) and IL-12 (increase in mRNA for IL-12 subunits p35 and p40). Changes in granulocytes seems not to rely on mitogen activated kinases p38 and ERK. Warfarin intake was associated with an increase in circulating IL-6, fibrinogen and haptoglobin and with changes in the activity of erythrocyte antioxidant enzymes superoxide dismutase and catalase. The effects of oral warfarin intake on peripheral blood granulocytes demonstrated in this study might be relevant for oral anticoagulant therapy strategies in humans.
authors.affiliation: Department of Ecology, Institute for Biological Research Siniša Stanković, University of Belgrade, Bulevar Despota Stefana 142, Belgrade, Serbia.
authors.forename: Sandra
authors.initials: S
authors.lastname: Belij
authors.forename: Djordje
authors.initials: D
authors.lastname: Miljković
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Popov
authors.forename: Vesna
authors.initials: V
authors.lastname: Subota
authors.forename: Gordana
authors.initials: G
authors.lastname: Timotijević
authors.forename: Marija
authors.initials: M
authors.lastname: Slavić
authors.forename: Ivana
authors.initials: I
authors.lastname: Mirkov
authors.forename: Dragan
authors.initials: D
authors.lastname: Kataranovski
authors.forename: Milena
authors.initials: M
authors.lastname: Kataranovski
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage* / Q000494:pharmacology; D001483:Base Sequence; D002374:Catalase / Q000378:metabolism; D002448:Cell Adhesion; D017931:DNA Primers; D004789:Enzyme Activation; D004797:Enzyme-Linked Immunosorbent Assay; D006098:Granulocytes / Q000166:cytology / Q000187:drug effects*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014859:Warfarin / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D000925:Anticoagulants; D017931:DNA Primers; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D014859:Warfarin; D002374:Catalase; D013482:Superoxide Dismutase; D011494:Protein Kinases