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

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.