Intestinal toxicity of oral warfarin intake in rats.
Food Chem Toxicol
; 94: 11-8, 2016 Aug.
Article
in En
| MEDLINE
| ID: mdl-27181730
ABSTRACT
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Warfarin
/
Intestines
/
Anticoagulants
Limits:
Animals
Language:
En
Journal:
Food Chem Toxicol
Year:
2016
Document type:
Article