Abstract

Lindane is an organochlorine pesticide widely used in veterinary and human medicine to treat ectoparasites and pediculosis. Given its lipophilic character lipid-rich membranes are a plausible target of its interaction with living organisms. To evaluate its toxic effect on cell membranes lindane was made to interact with human erythrocytes and molecular models of the red cell membrane. These consisted in bilayers of dimyristoylphosphatidylcholine (DMPC) and of dimyristoylphosphatidylethanolamine (DMPE), representative of phospholipid classes located in the outer and inner monolayers of the erythrocyte membrane, respectively. Experiments by fluorescence spectroscopy showed that lindane interacted with DMPC large unilamellar vesicles fluidizing both its polar head and its acyl chain regions. These results were confirmed by X-ray diffraction; however, a higher degree of structural perturbation was observed in DMPE bilayers. Electron microscopy of human erythrocytes incubated with lindane revealed that they changed their normal discoid shape to cup-shaped stomatocytes. In accordance with the bilayer couple hypothesis, this result means that lindane inserted in the inner leaflet of the erythrocyte membrane, in agreement with its preferential interaction with DMPE. It is therefore concluded that the toxic effects of the pesticide can be related to its capacity to interact with the lipid moiety of cell membranes.