Abstract

Heptachlor is an organochlorine pesticide which is particularly toxic for aquatic life. A significant source of this pesticide for infants is breast milk, where its concentration is considerably higher than in dairy milk. Given the lipophilic character of heptachlor, lipid-rich cell membranes are a very plausible target for its interaction with living organisms. In order to evaluate its toxicity towards cell membranes, heptachlor was made to interact with human erythrocytes and molecular models of the red cell membrane. These consisted of multilayers of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE), which are types of phospholipids that are respectively located in the outer and inner monolayers of the erythrocyte membrane, and large unilamellar vesicles (LUV) of DMPC. Observations by scanning electron microscopy showed that 10 mM heptachlor produced various degrees of shape alterations to erythrocytes, which ranged from a few blebs in some cells to a great number of protuberances in others. On the other hand, experiments performed by X-ray diffraction on DMPC and DMPE indicated that the bilayer structure of DMPC was much more affected by heptachlor than that of DMPE. Measurements by fluorescence spectroscopy on DMPC LW confirmed the X-ray diffraction results in that both the hydrocarbon chain and polar head regions of DMPC were structurally perturbed by heptachlor. The results obtained from the model studies could explain the shape changes induced to red cells by heptachlor. According to the bilayer hypothesis, they were due to the preferential interaction of heptachlor with the phosphatidylcholine-rich external moiety of the erythrocyte membrane. It is therefore concluded that toxic effects of this pesticide can be related to its capacity to perturb the phospholipid bilayer structure, whose integrity is essential for cell membrane functions.