Skin response to epicutaneous application of anticoagulant rodenticide warfarin is characterized by differential time- and dose-dependent changes in cell activity

Context: Skin is the target of both acute and chronic exposure to warfarin, coumarin anticoagulant. Single exposure of rat skin to this agent induces early (24?h following epicutaneous administration) local response which might be part of inflammatory/reparatory homeostatic program or introduction to pathological events in exposed skin.

Objective: To examine time-dependent changes in skin of rats exposed to epicutaneously applied warfarin.

Materials and methods: The effect of low (10?μg) and high (100?μg) doses of warfarin on histologically evident changes of epidermis (epidermal thickness) and dermis (numbers of mesenchymal cells and dermal capillaries), skin cell proliferative activity (Ki67⁺ and PCNA⁺ cells) and apoptotic (TUNEL⁺) and necrotic (ultra structural appearance) cells was examined one, three and seven days after the application.

Results: Both warfarin doses affected the majority of skin cell activity, but with differential time-course of skin epidermal and dermal cells state/activity. The occurrence of necrotic/apoptotic epidermal and dermal cells was noted the first day after the application and the activities which point to tissue reparation/remodeling were observed seven days after skin exposure to this agent.

Discussion: The observed pattern of changes (early evidence of cell/tissue injury which was later followed by signs of cell activity characteristic for tissue reparation/remodeling) implied warfarin-induced toxicity in skin cells as stimulus for subsequent activities relevant for tissue homeostasis.

Conclusion: The data presented provide new and additional information concerning skin responses to warfarin that gains access to this tissue.