Dermatotoxicity of epicutaneously applied anticoagulant warfarin.
Dermatotoxic effects of epicutaneous application of a first-generation anticoagulant, warfarin (WF) were examined in rats. Selected parameters of skin activity were determined 24h following warfarin application, including metabolic viability of skin explants, some aspects of oxidative activity in skin tissue homogenates and inflammatory/immune relevant activity of epidermal cells from warfarin-treated skin. No changes in skin metabolic viability (MTT reduction) were noted ex vivo following WF application, suggesting the absence of immediate toxicity for skin. In contrast, increased formation of malondialdehyde (MDA), with a decrease in protein and non-protein thiols in homogenates of warfarin-treated skin was demonstrated, pointing to prooxidant activity in warfarin-treated skin. Increased costimulatory activity of epidermal cells isolated from warfarin-exposed skin in Con-A-stimulated T-cell activation/proliferation assay was noted, reflecting proinflammatory and immune-modulating capacity of warfarin for epidermis. No evident differences in skin histology between control and warfarin-treated skin were found at that time point, while striking changes in tissue integrity, cellularity and appearance 72 h following WF application were noted. The observed histological picture probably reflects a regenerative/inflammatory program related to oxidant/inflammation-type warfarin-evoked injury to the skin. Presented data demonstrate the potential of epicutaneously applied warfarin to modulate local skin activity in rats.
Institute for Medical Research, Military Medical Academy, Crnotravska 17, 11000 Belgrade, Serbia and Montenegro. vmaimi@eunet.yu
Milena
M
Kataranovski
Vera
V
Prokić
Dragan
D
Kataranovski
Lidija
L
Zolotarevski
Ivana
I
Majstorović
D000279:Administration, Cutaneous; D000818:Animals; D000925:Anticoagulants / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects* / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014859:Warfarin / Q000633:toxicity*
D000925:Anticoagulants; D013438:Sulfhydryl Compounds; D017392:Thiobarbituric Acid Reactive Substances; D008315:Malondialdehyde; D014859:Warfarin; D005978:Glutathione