Intestinal toxicity of oral warfarin intake in rats
2016
Authors:
Mirkov, IvanaPopov Aleksandrov, Aleksandra
Demenesku, Jelena
Ninkov, Marina
Mileusnić, Dina
Zolotarevski, Lidija
Subota, Vesna
Kataranovski, Dragan
Kataranovski, Milena
Document Type:
Article (Published version)
,
© 2016 Elsevier Ltd.
Metadata
Show full item recordAbstract:
Though warfarin is extensively used in the prevention and treatment of thromboembolic
processes in humans, adverse effects of warfarin therapy have been recognized. Intestinal
hemorrhage is one of the hazards of anticoagulant therapy, but the mechanisms of warfarin
toxicity are virtually unknown. In this work, the effects of 30 days oral warfarin (0.35 mg/l and
3.5 mg/l) intake on rat’s gut were examined. Both doses resulted in prolongation of prothrombin
time. Systemic effects of higher warfarin dose (increases in plasma AST, proteinuria, hematuria,
changes in peripheral blood hematological parameters) were seen. Warfarin intake resulted in
histologically evident tissue damage, leukocyte infiltration and intestinal inflammation [increases
in myeloperoxidase activity, malondialdehyde content, superoxide dismutase and catalase
activity, proinflammatory cytokine (IFN-γ, IL-17) concentrations in intestinal homogenates]. In
contrast, suppression of gut-draining mesenteric lymph node (MLN) cell activity [proliferation
responsiveness, production of IFN-γ and IL-17 to T lymphocyte mitogen Concanavalin A
stimulation] was noted. Inhibition of regulatory cytokine IL-10 production by MLN cells,
suggests commitment of MLN to the suppression of all inflammatory activities and creation of
the microenvironment which is non-permissive for induction of potentially harmful immune
response. These novel findings indicate the need of staying alert for (adverse) effects of warfarin
therapy.
Keywords:
Oral warfarin intake; Rats; Intestinal inflammation; Mesenteric lymph nodesSource:
Food and Chemical Toxicology, 2016, 94, 11-18Funding / projects:
- Immunomodulatory effects of environmental xenobiotics and biotic factors on the populations of mouse-like rodents (RS-MESTD-Basic Research (BR or ON)-173039)
DOI: 10.1016/j.fct.2016.05.007
ISSN: 0278-6915
PubMed: 27181730