Abstract

Methylation of inorganic arsenic has been regarded as a detoxification mechanism because its metabolites monomethylarsonic acid (MMAv) and dimethylarsinic acid (DMAv) are supposed to be less toxic than inorganic arsenite and arsenate. In recent years, however, this interpretation has been questioned. Additionally, there are insufficient reports concerning the effects of arsenic compounds on cell membrane structure and functions. With the aim to better understand the molecular mechanisms of the interaction of MMAv and arsenate with cell membranes, we have utilized molecular models consisting in bilayers of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE), representative of phospholipid classes located in the outer and inner monolayers of many cell membranes including that of the human erythrocyte. The capacity of MMAv and arsenate to perturb the bilayer structures of DMPC and DMPE was evaluated by X-ray diffraction; the modifications of their thermotropic behavior were followed by differential scanning calorimetry (DSC), while DMPC large unilamellar vesicles (LUV) were studied by fluorescence spectroscopy. It was found that MMAv and arsenate did not structurally perturb DMPC bilayers; however, DMPE bilayers did suffer structural perturbations by MMAv. DSC measurements also revealed that DMPE's thermotropic properties were significantly affected by arsenicals, where MMAv was more effective than arsenate, whilst only slight modifications were observed in the case of DMPC-MMAv system. © 2007 Elsevier B.V. All rights reserved.