Kataranovski Milena, Mirkov Ivana, Vrankovic Jelena, Kataranovski Dragan, Subota Vesna
Department of Ecology, Institute for Biological Research "S. Stankovic," Belgrade, Serbia.
Cutan Ocul Toxicol. 2008;27(1):29-40. doi: 10.1080/15569520701860999.
Percutaneous toxicity of anticoagulant rodenticides is usually manifested by coagulopathy and/or fatal outcome. There are, however, virtually no data on other biological effects of this class of pesticides that gain access into the organism via skin. In this study, percutaneous toxicity of epicutaneously applied warfarin was evaluated by measuring changes in peripheral blood granulocytes in rats. Application of 10 mug (0.05 mg/kg) or 100 mug (0.5 mg/kg) of warfarin (WF) for 3 consecutive days resulted in an increase in prothrombin time, documenting the access of warfarin to systemic circulation. Application of warfarin led to an increase in relative numbers of granulocytes at higher dose, whereas both doses resulted in increased metabolical viability, evaluated by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) reduction assay. Higher warfarin dose resulted in both granulocyte activation and priming (evaluated by cytochemical nitroblue tetrazolium, NBT, reduction assay of respiratory burst), whereas only a tendency toward activation was noted at lower WF dose. Soluble mediators from the circulation seem responsible for the observed effects, as exogenous plasma from WF-treated animals stimulated NBT reduction by isologous or naïve granulocytes. Data presented in this study are relevant for the recognition of biological effects, other than those affecting hemostasis, of anticoagulant rodenticides that gain access to systemic circulation through the skin.
抗凝血灭鼠剂的经皮毒性通常表现为凝血病和/或致命后果。然而，关于这类通过皮肤进入机体的杀虫剂的其他生物学效应，实际上几乎没有数据。在本研究中，通过测量大鼠外周血粒细胞的变化来评估经皮应用华法林的经皮毒性。连续3天应用10微克（0.05毫克/千克）或100微克（0.5毫克/千克）的华法林（WF）导致凝血酶原时间延长，证明华法林进入了体循环。应用华法林在较高剂量时导致粒细胞相对数量增加，而两种剂量均导致代谢活力增加，通过3-（4,5-二甲基-2-噻唑基）-2,5-二苯基-2H-四氮唑溴盐（MTT）还原试验进行评估。较高剂量的华法林导致粒细胞活化和预激（通过细胞化学硝基蓝四氮唑（NBT）还原试验评估呼吸爆发），而在较低的WF剂量下仅观察到活化趋势。循环中的可溶性介质似乎是观察到的效应的原因，因为来自经WF处理动物的外源性血浆刺激同源或未接触过的粒细胞的NBT还原。本研究中呈现的数据对于认识通过皮肤进入体循环的抗凝血灭鼠剂除影响止血之外的生物学效应具有重要意义。
