warfarin and Dermatitis--Contact

Topics: Chamomile; Colic; Conjunctivitis; Cyclosporine; Dermatitis; Dermatitis, Contact; Diarrhea; Dyspepsia; Female; Flowers; Herb-Drug Interactions; Humans; Infant; Lactation; Morning Sickness; Phytotherapy; Plant Extracts; Plant Preparations; Pregnancy; Warfarin

To evaluate the effects of epicutaneous application of anticoagulant warfarin, by examining the presence of tissue injury and immune/inflammatory activity in exposed skin.. Rats were exposed to warfarin by applying 10 μg of warfarin-sodium to 10-12 cm(2) skin (range 0.8-1 μg per 1 cm(2)) for 3 consecutive days. Tissue injury was evaluated by lipid peroxidation, histomorphological changes and signs of reparative activity in skin. T cell infiltration and selected aspects of epidermal cell activity were examined as indicators of immune/inflammatory skin response to warfarin application.. Repeated warfarin application exerted no effect on skin metabolic viability, but resulted in tissue injury (increased malondialdehyde, MDA, production, evident histo-morphological changes in epidermis and dermis depicting cell injury and death). Increased numbers of proliferating cell nuclear antigen (PCNA(+)) cells indicated reparative processes in injured skin. Infiltration of CD3(+) cells (T lymphocytes) along with the increased production of tumor necrosis factor-a (TNF-a) by epidermal cells from warfarin-treated skin and their co-stimulatory effect in an in vitro T-cell activation assay demonstrated immunomodulatory effects of epicutaneous warfarin.. Presented data have documented tissue damage associated with immune/inflammatory activity in skin exposed to warfarin. Observed effects are relevant to immunotoxic potential of this anticoagulant in settings of external exposure.

Topics: Animals; CD3 Complex; Dermatitis, Contact; Epidermal Cells; Gene Expression Regulation; Inflammation; Lipid Peroxidation; Male; Proliferating Cell Nuclear Antigen; Rats; Rodenticides; Skin; T-Lymphocytes; Warfarin

The immunotoxicity of epicutaneously administered anticoagulant rodenticide warfarin (WF) was examined in this work by using experimental contact hypersensitivity (CHS) reaction to hapten dinitrochlorobenzene (DNCB). WF (0.05 and 0.5 mg/kg) administration 24 h before the induction of CHS does not change expression of CHS evaluated by ear swelling assay. Regional draining lymph node response during sensitization phase was characterized by decreased cellularity but increased spontaneous and IL-2 stimulated proliferation of draining lymph node cells (DLC). No changes in IL-2 production and in numbers of CD25(+) cells were noted and even decreased proliferative index (ratio of IL-2 stimulated to unstimulated DLC proliferation) was detected. Increase in granulocyte activity (MTT reduction and adhesion to plastic) was noted following application of WF solely with further increase following subsequent application of DNCB, when granulocyte activation (NBT reduction) was noted also. Access of WF into general circulation might be responsible for observed changes, what was supported by ex vivo changes in DLC and granulocyte functions assessed before initiation of sensitization and by in vitro effect of exogenous WF as well. Differential effects of WF on lymphocytes and granulocytes noted in this study highlight the need for simultaneous testing of both cell type activity what might constitute a more integrated approach in immunotoxicity studies.

Topics: Administration, Topical; Animals; Anticoagulants; Cell Adhesion; Dermatitis, Contact; Dinitrochlorobenzene; Formazans; Granulocytes; Interleukin-2; Irritants; Lymph Nodes; Lymphocyte Activation; Male; Partial Thromboplastin Time; Prothrombin Time; Rats; Receptors, Interleukin-2; Rodenticides; Tetrazolium Salts; Warfarin