- 作者：Aleksandra POPOVa ; Ivana MIRKOVa ; Lidija ZOLOTAREVSKIb ; Milena JOVICb ; Sandra BELIJa ; Dragan KATARANOVSKIa ; c ; Milena KATARANOVSKIa ; d ; milena@ibiss.bg.ac.rs"" rel=""nofollow [Author vitae]
- 关键词：Rats ; Warfarin ; Epicutaneous exposure ; Tissue damage ; Skin inflammation
- 刊名：Biomedical and Environmental Sciences
- 出版年：2011
- 出版时间：April 2011
- 年：2011
- 卷：24
- 期：2
- 页码：180-189
- 全文大小：568 K
ObjectiveTo evaluate the effects of epicutaneous application of anticoagulant warfarin, by examining the presence of tissue injury and immune/inflammatory activity in exposed skin.Methods
Rats were exposed to warfarin by applying 10 μg of warfarin-sodium to 10-12 cm2 skin (range 0.8-1 μg per 1 cm2) 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.
Results
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.
Conclusion
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.