The Pesticide Hexachlorobenzene Induces Alterations in the Human Erythrocyte Membrane

Abstract

Hexachlorobenzene (HCB) is one of the most widely distributed organochlorine residues in the biosphere. High concentrations have been found in developing and industrialized countries. Due to its persistence in the environment it has been detected in fish, birds, eggs, and human adipose tissue and serum, and chronic administration of this compound causes a number of toxic effects. Due to the lipophilic character of HCB, lipid-rich membranes are important targets for its interaction with living organisms. HCB was incubated with human erythrocytes and molecular models of biomembranes in order to better understand the molecular mechanism of its interaction with cell membranes. The models consisted of bilayers of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE), representative of phospholipid classes located in the outer and inner monolayers of the human erythrocyte membrane, respectively. Electron microscopy showed that HCB interacted with the erythrocyte membrane, modifying its normal discoid morphology to cup-shaped stomatocytes. This result indicates that HCB was inserted in the inner layer of the red cell membrane, a conclusion supported by X-ray diffraction analyses of DMPC and DMPE bilayers. In fact, HCB incorporated into and perturbed the bilayer structures of DMPC and DMPE. However, the extent of the interaction was higher in DMPE. Therefore, the experimental results confirmed the important role played by the phospholipid bilayer in the molecular mechanism of HCB interaction with the red cell membrane.