Local proinflammatory effects of repeated skin exposure to warfarin, an anticoagulant rodenticide in rats.
- Author:
Aleksandra POPOV
1
;
Ivana MIRKOV
;
Lidija ZOLOTAREVSKI
;
Milena JOVIC
;
Sandra BELIJ
;
Dragan KATARANOVSKI
;
Milena KATARANOVSKI
Author Information
- Publication Type:Journal Article
- MeSH: Animals; CD3 Complex; genetics; metabolism; Dermatitis, Contact; pathology; Epidermis; cytology; Gene Expression Regulation; physiology; Inflammation; metabolism; Lipid Peroxidation; Male; Proliferating Cell Nuclear Antigen; genetics; metabolism; Rats; Rodenticides; pharmacology; Skin; cytology; drug effects; metabolism; T-Lymphocytes; physiology; Warfarin; pharmacology
- From: Biomedical and Environmental Sciences 2011;24(2):180-189
- CountryChina
- Language:English
-
Abstract:
OBJECTIVETo evaluate the effects of epicutaneous application of anticoagulant warfarin, by examining the presence of tissue injury and immune/inflammatory activity in exposed skin.
METHODSRats 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.
RESULTSRepeated 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.
CONCLUSIONPresented 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.
