Subota Vesna, Mirkov Ivana, Demenesku Jelena, Popov Aleksandrov Aleksandra, Ninkov Marina, Mileusnic Dina, Kataranovski Dragan, Kataranovski Milena
Institute for Medical Biochemistry, Military Medical Academy, Crnotravska 17, 11000 Belgrade, Serbia.
Department of Ecology, Institute for Biological Research "Sinisa Stankovic", University of Belgrade, Bulevar despota Stefana 142, 11000 Belgrade, Serbia.
Environ Toxicol Pharmacol. 2016 Jan;41:232-40. doi: 10.1016/j.etap.2015.12.006. Epub 2015 Dec 17.
Occupational/accidental exposure data have showed hemorrhage as a result of transdermal exposure to warfarin, however, other effects are not known. In the present study, the impact of epicutaneous application of 10 μg or 100 μg of warfarin (three times, once a day) on peripheral blood polymorphonuclear (PMN) and mononuclear cells (PBMC) was examined in rats. Both doses resulted in prolongation of prothrombin time and changes in hematologic parameters. Increases in PMN intracellular myeloperoxidase (MPO) activity were seen at higher warfarin dose and both doses resulted in higher percentages of granular CD11b(+) cells. In contrast, a decrease in PMN TNF and IL-6 production (ELISA) and gene expression (RT-PCR) was observed. Epicutaneous application of warfarin resulted in decreased numbers of PBMC, higher numbers of mononuclear CD11b(+) cells, but without effect on PMBC cytokine production. The data obtained showed differential effects of transdermal exposure to warfarin depending on leukocyte type and activity.
职业性/意外暴露数据显示，经皮接触华法林会导致出血，然而，其他影响尚不清楚。在本研究中，对大鼠经皮涂抹10μg或100μg华法林（每天一次，共三次）对外周血多形核（PMN）细胞和单核细胞（PBMC）的影响进行了检测。两种剂量均导致凝血酶原时间延长和血液学参数改变。在较高华法林剂量下，PMN细胞内髓过氧化物酶（MPO）活性增加，且两种剂量均导致颗粒状CD11b(+)细胞百分比升高。相反，观察到PMN肿瘤坏死因子（TNF）和白细胞介素-6（IL-6）的产生（酶联免疫吸附测定）及基因表达（逆转录-聚合酶链反应）下降。经皮涂抹华法林导致PBMC数量减少，单核CD11b(+)细胞数量增加，但对PMBC细胞因子产生无影响。所获得的数据显示，经皮接触华法林对不同白细胞类型和活性有不同影响。
