ABSTRACT
<p><b>OBJECTIVE</b>To evaluate the effects of epicutaneous application of anticoagulant warfarin, by examining the presence of tissue injury and immune/inflammatory activity in exposed skin.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>
Subject(s)
Animals , Male , Rats , CD3 Complex , Genetics , Metabolism , Dermatitis, Contact , Pathology , Epidermis , Cell Biology , Gene Expression Regulation , Physiology , Inflammation , Metabolism , Lipid Peroxidation , Proliferating Cell Nuclear Antigen , Genetics , Metabolism , Rodenticides , Pharmacology , Skin , Cell Biology , Metabolism , T-Lymphocytes , Physiology , Warfarin , PharmacologyABSTRACT
<p><b>OBJECTIVE</b>To examine the presence of gender differences in pulmonary inflammation evoked by acute systemic cadmium administration in rats.</p><p><b>METHODS</b>Presence of basic indicators of lung inflammation (inflammatory cytokine lung content, leukocyte infiltration and activity of cells recovered from lungs by enzyme digestion) was analyzed and compared in animals of the two sexes.</p><p><b>RESULTS</b>Intraperitoneal administration of cadmium (1.0 mg/kg) resulted in higher cadmium content in lungs of female rats. Higher tumor necrosis factor (TNF) content was noted in lung homogenates of male rats, while interleukin-6 (IL-6) content was slightly, but significantly greater in lungs of female rats. Increased leukocyte infiltration was observed in lungs of male rats, mainly due to neutrophils. Increased responsiveness to phorbol myristate acetate (PMA) stimulation was noted in cells recovered from lungs of male rats. Rise in intracellular content of myeloperoxidase (MPO) was noted in lung cells from cadmium-treated rats of both sexes, but higher in cells from male rats.</p><p><b>CONCLUSIONS</b>Presented data documented a more intense pulmonary inflammatory response to systemic cadmium administration in males, with higher IL-6 levels in lungs of female individuals. These sex differences in proinflamatory activity of cadmium in lungs should be taken into consideration in studying the remote toxicity of this heavy metal.</p>
Subject(s)
Animals , Female , Male , Rats , Cadmium Chloride , Pharmacokinetics , Toxicity , Cytokines , Allergy and Immunology , Environmental Pollutants , Pharmacokinetics , Toxicity , Enzyme-Linked Immunosorbent Assay , Leukocyte Count , Leukocytes , Cell Biology , Allergy and Immunology , Lung , Allergy and Immunology , Metabolism , Neutrophil Infiltration , Allergy and Immunology , Peroxidase , Metabolism , Pneumonia , Allergy and Immunology , Metabolism , Rats, Inbred Strains , Sex CharacteristicsABSTRACT
<p><b>OBJECTIVE</b>To examine the presence of gender differences in pro-inflammatory potential of cadmium in rats by comparing systemic inflammatory response to acute cadmium intoxication in animals of the two sexes.</p><p><b>METHODS</b>Basic aspects of this response were evaluated, including plasma levels of inflammatory cytokines tumor necrosis factor (TNF) and interleukin-6 (IL-6) and of major rat acute phase protein alpha 2-macroglobulin (alpha2-M), as soluble indicators of inflammation, and the number and activity of peripheral blood leukocytes, as cellular indicators of inflammation.</p><p><b>RESULTS</b>Differential increases of IL-6 and alpha2-M (higher in males than in females) in peripheral blood cell counts and types (leukocytosis and shift in the ratio of granulocytes to lymphocytes more pronounced in males vs females) and in levels of neutrophil priming (higher in males vs females) were noted.</p><p><b>CONCLUSION</b>The data document a more intense inflammatory response to cadmium administration in males. The sex differences in inflammatory effects of cadmium might be taken into consideration in studying the toxicity of this heavy metal.</p>