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有机锡在红细胞膜内的位置与其毒性的关系。

The location of organotins within the erythrocyte membrane in relation to their toxicity.

机构信息

Department of Physics and Biophysics, WrocŁaw University of Environmental and Life Sciences, Norwida 25, 50-375 WrocŁaw, Poland.

出版信息

Ecotoxicol Environ Saf. 2012 Apr;78:232-8. doi: 10.1016/j.ecoenv.2011.11.027. Epub 2011 Dec 5.

DOI:10.1016/j.ecoenv.2011.11.027
PMID:22153305
Abstract

The aim of the present study on organotin compounds, which are toxic to biological systems, was to determine the relationship between the compounds' toxicity and their location in the lipid bilayer of the biological membrane. It was assumed that the degree of disturbance caused within the lipid bilayer of the membrane, which in turn depends on the depth of incorporation, was an appropriate measure of toxicity. Previous results from our studies on the effect of organotin chlorides on membranes, made by using infrared radiation and hemolysis of erythrocytes, indicated that tributyltin (TBT) is the most active in terms of its interaction with the erythrocyte membrane. This compound causes the most severe hemolysis of erythrocytes and dehydration of membrane constituents. In order to connect the changes induced within the membrane structure with the compounds' location, we have investigated erythrocyte shape changes using both microscopic and fluorimetric methods. The microscopic results show that organotin compounds accumulate in the outer monolayer of the membrane. The fluorimetric studies indicate that all the compounds are present in the hydrophilic part of the outer lipid monolayer, and change the order parameter of the layer. However, only tributyltin, by being incorporated into the hydrophobic region of the monolayer, changes the fluidity in the alkyl chain region of the erythrocyte membrane. Furthermore, only TBT is present in both the hydrophilic and hydrophobic regions, as evidenced by the changed order parameter of the polar groups and fluorescence anisotropy of DPH probe in the hydrophobic region, these being connected with its high toxicity.

摘要

本研究旨在探讨有机锡化合物(对生物系统具有毒性)的毒性与其在生物膜脂质双层中的位置之间的关系。研究假设,膜脂质双层内的干扰程度(取决于其整合深度)是衡量毒性的一个恰当指标。我们之前的研究结果表明,有机锡氯化物对细胞膜的影响,通过使用红外辐射和红细胞溶血实验可以得到,其中三丁基锡(TBT)在与红细胞膜的相互作用方面表现出最强的活性。该化合物可导致红细胞严重溶血和膜成分脱水。为了将膜结构内的变化与化合物的位置联系起来,我们使用显微镜和荧光法研究了红细胞形态的变化。显微镜结果表明,有机锡化合物在膜的外层单层中积累。荧光研究表明,所有化合物都存在于外层脂质单层的亲水区,并改变了层的序参数。然而,只有三丁基锡通过整合到单层的疏水区,才会改变红细胞膜烷基链区域的流动性。此外,只有 TBT 存在于亲水区和疏水区,这可以从极性基团的变化序参数和 DPH 探针在疏水区的荧光各向异性得到证明,这些都与它的高毒性有关。

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