Effects of subacute oral warfarin administration on peripheral blood granulocytes in rats
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2012
Authors
Belij, SandraMiljković, Djordje
Popov, Aleksandra
Subota, Vesna
Timotijević, Gordana
Slavić, Marija
Mirkov, Ivana
Kataranovski, Dragan
Kataranovski, Milena
Article (Published version)
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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 3.5 mg/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-alpha (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 p...38 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.
Keywords:
Rats / Peripheral blood granulocytes / Oral warfarin intake / InflammationSource:
Food and Chemical Toxicology, 2012, 50, 5, 1499-1507Publisher:
- Pergamon-Elsevier Science Ltd, Oxford
Funding / projects:
- Immunomodulatory effects of environmental xenobiotics and biotic factors on the populations of mouse-like rodents (RS-MESTD-Basic Research (BR or ON)-173039)
- Cellular and molecular mechanisms of recovery of rats from experimental autoimmune encephalomyelitis (RS-MESTD-Basic Research (BR or ON)-173035)
DOI: 10.1016/j.fct.2012.01.049
ISSN: 0278-6915
PubMed: 22342526
WoS: 000304572000042
Scopus: 2-s2.0-84858259009
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Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Belij, Sandra AU - Miljković, Djordje AU - Popov, Aleksandra AU - Subota, Vesna AU - Timotijević, Gordana AU - Slavić, Marija AU - Mirkov, Ivana AU - Kataranovski, Dragan AU - Kataranovski, Milena PY - 2012 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/545 AB - 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 3.5 mg/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-alpha (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. PB - Pergamon-Elsevier Science Ltd, Oxford T2 - Food and Chemical Toxicology T1 - Effects of subacute oral warfarin administration on peripheral blood granulocytes in rats EP - 1507 IS - 5 SP - 1499 VL - 50 DO - 10.1016/j.fct.2012.01.049 ER -
@article{ author = "Belij, Sandra and Miljković, Djordje and Popov, Aleksandra and Subota, Vesna and Timotijević, Gordana and Slavić, Marija and Mirkov, Ivana and Kataranovski, Dragan and Kataranovski, Milena", year = "2012", 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 3.5 mg/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-alpha (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.", publisher = "Pergamon-Elsevier Science Ltd, Oxford", journal = "Food and Chemical Toxicology", title = "Effects of subacute oral warfarin administration on peripheral blood granulocytes in rats", pages = "1507-1499", number = "5", volume = "50", doi = "10.1016/j.fct.2012.01.049" }
Belij, S., Miljković, D., Popov, A., Subota, V., Timotijević, G., Slavić, M., Mirkov, I., Kataranovski, D.,& Kataranovski, M.. (2012). Effects of subacute oral warfarin administration on peripheral blood granulocytes in rats. in Food and Chemical Toxicology Pergamon-Elsevier Science Ltd, Oxford., 50(5), 1499-1507. https://doi.org/10.1016/j.fct.2012.01.049
Belij S, Miljković D, Popov A, Subota V, Timotijević G, Slavić M, Mirkov I, Kataranovski D, Kataranovski M. Effects of subacute oral warfarin administration on peripheral blood granulocytes in rats. in Food and Chemical Toxicology. 2012;50(5):1499-1507. doi:10.1016/j.fct.2012.01.049 .
Belij, Sandra, Miljković, Djordje, Popov, Aleksandra, Subota, Vesna, Timotijević, Gordana, Slavić, Marija, Mirkov, Ivana, Kataranovski, Dragan, Kataranovski, Milena, "Effects of subacute oral warfarin administration on peripheral blood granulocytes in rats" in Food and Chemical Toxicology, 50, no. 5 (2012):1499-1507, https://doi.org/10.1016/j.fct.2012.01.049 . .