Molecular mechanism of haemolysis induced by triphenyltin chloride

Organometals are known to cause lysis of cells, but the molecular mechanism of their action is not recognized. In this work, we have examined the interaction of triphenyltin with erythrocyte membranes. We determined the order of haemolytic activity of the investigated organometal species as being: triphenyllead > tripropyltin = triphenyltin > triethyllead > trimethyltin. Such an order suggests that the haemolytic activity increases with the increasing hydrophobicity of the organic ligands. Compounds containing lead are more toxic than the respective complexes of tin. Triphenyltin chloride (Ph3SnCl) is very effective in lysis of erythrocytes. Using Sn-119 Mossbauer spectroscopy we showed that triphenyltin interacts with the protein components of pig erythrocyte membranes in a highly specific way, but we did not detect any interaction of triphenyltin with pig haemoglobin. The Mossbauer spectrum was fitted with a single doublet characterized by hyperfine parameters that differ considerably from those reported for other organotin compounds in membranes of red blood cells. Applying the point charge model of the electric field gradient for the analysis of the environment of tin bonds from the quadrupole splitting, we could indicate N-het from histidine and/or S-thiol from cysteine as the only possible ligands of Ph3Sn(IV). We expect that protein components of erythrocyte membranes having similar cysteine and histidine arrangement, such as in cat or rat haemoglobins, which provide high-affinity binding sites for organotins, can bind triphenyltin with high affinity. We give some arguments that ankyrin and beta-spectrin are the most probable targets of Ph3Sn(IV) action and indicate its potential binding sites within the proteins. The highly specific interaction of triphenyltin with the membrane cytoskeleton. components, postulated by us, should already influence the rigidity of red blood cells at the stage preceding the lysis of erythrocytes. To support this hypothesis, we carried out scanning force microscopy measurements of red blood cells elasticity. We have observed a lower stiffness for erythrocytes treated with concentrations of Ph3SnCl that caused less than 20% of haemolysis. Copyright (C) 2002 John Wiley Sons, Ltd.