Department of Ecology, University of Belgrade, 11000 Belgrade, Serbia.
Biomed Environ Sci. 2011 Apr;24(2):180-9. doi: 10.3967/0895-3988.2011.02.013.
To evaluate the effects of epicutaneous application of anticoagulant warfarin, by examining the presence of tissue injury and immune/inflammatory activity in exposed skin.
Rats 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.
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.
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.
通过检测暴露皮肤的组织损伤和免疫/炎症活性，评估经皮应用抗凝剂华法林的效果。
将 10μg 的华法林钠应用于 10-12cm²（每 1cm² 为 0.8-1μg）的皮肤，连续 3 天，使大鼠接触华法林。通过脂质过氧化、皮肤组织学变化和修复活性的迹象来评估组织损伤。浸润的 T 细胞和表皮细胞活动的特定方面被视为华法林应用于皮肤的免疫/炎症反应的指标。
重复应用华法林对皮肤代谢活力没有影响，但会导致组织损伤（增加丙二醛 MDA 的产生，表皮和真皮的明显组织形态变化表明细胞损伤和死亡）。增殖细胞核抗原（PCNA(+））细胞数量的增加表明受损皮肤的修复过程。来自华法林处理皮肤的表皮细胞中 CD3(+)细胞（T 淋巴细胞）的浸润以及肿瘤坏死因子-α（TNF-a）的增加产生及其在体外 T 细胞激活试验中的共刺激作用，证明了经皮华法林的免疫调节作用。
本研究数据记录了暴露于华法林的皮肤与免疫/炎症活性相关的组织损伤。观察到的效应与这种抗凝剂在外部暴露环境中的免疫毒性潜力相关。
