Abstract

Gold is a non-essential element extensively used in a variety of applications in medicine. Au(I) compounds have been widely used to treat rheumatoid arthritis, whereas a number of Au(III) derivatives have been prepared and assessed as potential anticancer agents. Gold compounds are well known for their nephrotoxic and neurological implications; however, hematologic toxicity is one of the most serious toxic effects. The lack of information on both neurotoxic and hematotoxic aspects of Au(III) prompted us to study the structural effects of tetrachloroauric acid (HAuCl 4) on cell membranes, particularly that of human erythrocytes. In order to better understand the molecular mechanisms of its interaction with cell membranes, a preparation of human red cells and molecular models of the erythrocyte membrane has been used. The molecular 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. The capacity of HAuCl 4 to perturb the bilayer structures of DMPC and DMPE was evaluated by X-ray diffraction, while large unilamellar vesicles (LUVs) of DMPC were analyzed by fluorescence spectroscopy. The effect of HAuCl 4 was also examined on the morphology of intact human erythrocytes by scanning electron microscopy (SEM), whereas isolated unsealed human erythrocyte membranes (IUM) were studied by fluorescence spectroscopy. In addition, to better understand gold toxicity in the brain, the effect of a chronic treatment with HAuCl 4 is herein reported with immunohistochemical evaluations. © 2009 Elsevier B.V. All rights reserved.