Cadmium-induced changes in the membrane of human erythrocytes and molecular models M. Suwalsky a, * , F. Villena b , B. Norris b , F. Cuevas c , C.P. Sotomayor c a Department of Polymers, Faculty of Chemical Sciences, University of Concepcion, E. Larenas 129, Casilla 160-C, Concepcion, Chile b Faculty of Biological Sciences, University of Concepcion, Casilla 160-C, Concepcion, Chile c Institute of Chemistry, Catholic University of Valparaiso, Valparaiso, Chile Received 31 December 2003; received in revised form 24 February 2004; accepted 28 February 2004 Available online 25 March 2004 Abstract The structural effects of cadmium on cell membranes were studied through the interaction of Cd 2þ ions with human erythrocytes and their isolated unsealed membranes (IUM). Studies were carried out by scanning electron microscopy and fluorescence spec- troscopy, respectively. Cd 2þ induced shape changes in erythrocytes, which took the form of echinocytes. According to the bilayer couple hypothesis, this result meant that Cd 2þ ions located in the outer monolayer of the erythrocyte membrane. Fluorescence spectroscopy measurements in IUM indicated a disordering effect at both the polar headgroup and the acyl chain packing ar- rangements of the membrane phospholipid bilayer. Cd 2þ ions also interacted with molecular models of the erythrocyte membrane consisting in bilayers of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE), representing classes of phospholipids located in the outer and inner monolayers the erythrocyte membrane, respectively. X-ray diffraction in- dicated that Cd 2þ ions induced structural perturbation of the polar headgroup and of the hydrophobic acyl regions of DMPC, while the effects of cadmium on DMPE bilayers were much milder. This conclusion is supported by fluorescence spectroscopy mea- surements on DMPC large unilamellar vesicles (LUV). All these findings point to the important role of phospholipid bilayers in the interaction of cadmium on cell membranes. Ó 2004 Elsevier Inc. All rights reserved. Keywords: Cadmium ions; Erythrocyte membrane; Phospholipid bilayer 1. Introduction Cadmium is not only a non-essential metal but is among the most toxic environmental pollutants induc- ing a broad spectrum of toxicological and biochemical dysfunctions constituting a serious hazard to health. Cadmium is a multitarget toxicant for most organisms, causing severe damage to lung, liver, kidney, testis and placenta [1]. It can induce cell death either by necrotic or by apoptotic mechanisms [2]. Exposure to cadmium results in neuropathological and neurochemical altera- tions in the central nervous system; this metal is a potent inhibitor of brain (Na þ –K þ ) and Mg 2þ -ATPase, inhib- its choline transport in synaptosomes and the release of neurotransmitters [3]. Cadmium is absorbed into blood circulation through metal transporters, the hematologi- cal system being one of the targets of Cd 2þ toxicity. Cadmium has a similar ionic radius to that of calcium while its electronegativity is similar to that of zinc. These properties allow Cd 2þ to enter cells and therefore is potentially able to interfere with the physiological functions of both calcium and zinc. It has been reported that this pollutant can induce anemia, alteration of an- tioxidant and metabolic status of erythrocytes, increase lipid peroxidation and hemoglobin content, alter the membrane skeleton [4], inhibit the erythrocyte Na  ,K þ - ATPase and Ca 2þ -dependent K þ channels [5]. Although the toxicity of this metal has been well established in vivo and in vitro, the mechanisms involved in membrane physiology remain unclear [6]. * Corresponding author. Tel.: +56-41-204171; fax: +56-41-245974. E-mail address: msuwalsk@udec.cl (M. Suwalsky). 0162-0134/$ - see front matter Ó 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.jinorgbio.2004.02.027 Journal of Inorganic Biochemistry 98 (2004) 1061–1066 www.elsevier.com/locate/jinorgbio JOURNAL OF Inorganic Biochemistry