title: Epicutaneous exposure to anticoagulant rodenticide warfarin modulates local skin activity in rats.
abstract: Dermatotoxic effects of epicutaneous application of a first generation anticoagulant, warfarin (WF), were examined in rats. Selected parameters of skin activity were determined 24 hours following warfarin application by histomorphological and immunohistochemical analysis and by assessing some aspects of immunomodulatory potential of warfarin in skin. Increased number of mast cells, with degranulation at higher doses of warfarin was noted in warfarin treated skin. Mast cell presence coincided with changes in blood vessels and fibroblast appearance suggesting mast cell activity in warfarin treated skin. Signs of nuclear hypertrophy and anysonucleosys were noted by analysis of PCNA(+) cells in epidermis following warfarin application. Histomorphological changes were accompanied by immunemodulating activity in warfarin treated skin. This was judged by slightly increased numbers of CD3(+) cells in epidermis and superficial dermis and by production of organ cultured full thickness skin explants of factors with costimulatory activity in T-cell activation/proliferation assay. Presented data demonstrates the potential of warfarin to modulate local skin activity in rats.
authors.affiliation: Department of Ecology, Institute for Biological Research S. Stankovic, Bul. Despota Stefana, Belgrade, Serbia and Montenegro. milena@ibiss.bg.ac.yu
authors.forename: Milena
authors.initials: M
authors.lastname: Kataranovski
authors.forename: Dragan
authors.initials: D
authors.lastname: Kataranovski
authors.forename: Lidija
authors.initials: L
authors.lastname: Zolotarevski
authors.forename: Milena
authors.initials: M
authors.lastname: Jovic
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D017252:CD3 Complex / Q000032:analysis / Q000187:drug effects; D015550:Cell Degranulation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003208:Concanavalin A / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007120:Immunochemistry; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology; D008934:Mitogens / Q000494:pharmacology; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D012378:Rodenticides / Q000633:toxicity*; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects; D046509:Tissue Culture Techniques; D018675:Toxicity Tests / Q000379:methods; D014859:Warfarin / Q000633:toxicity*
chemical_list: D017252:CD3 Complex; D008934:Mitogens; D018809:Proliferating Cell Nuclear Antigen; D012378:Rodenticides; D003208:Concanavalin A; D014859:Warfarin