title: Oxidative stress due to aluminum exposure induces eryptosis which is prevented by erythropoietin.
abstract: The widespread use of aluminum (Al) provides easy exposure of humans to the metal and its accumulation remains a potential problem. In vivo and in vitro assays have associated Al overload with anemia. To better understand the mechanisms by which Al affects human erythrocytes, morphological and biochemical changes were analyzed after long-term treatment using an in vitro model. The appearance of erythrocytes with abnormal shapes suggested metal interaction with cell surface, supported by the fact that high amounts of Al attached to cell membrane. Long-term incubation of human erythrocytes with Al induced signs of premature erythrocyte death (eryptosis), such as phosphatidylserine externalization, increased intracellular calcium, and band 3 degradation. Signs of oxidative stress, such as significant increase in reactive oxygen species in parallel with decrease in the amount of reduced glutathione, were also observed. These oxidative effects were completely prevented by the antioxidant N-acetylcysteine. Interestingly, erythrocytes were also protected from the prooxidative action of Al by the presence of erythropoietin (EPO). In conclusion, results provide evidence that chronic Al exposure may lead to biochemical and morphological alterations similar to those shown in eryptosis induced by oxidant compounds in human erythrocytes. The antieryptotic effect of EPO may contribute to enhance the knowledge of its physiological role on erythroid cells. Irrespective of the antioxidant mechanism, this property of EPO, shown in this model of Al exposure, let us suggest potential benefits by EPO treatment of patients with anemia associated to altered redox environment.
authors.affiliation: Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón II, Piso 4, Ciudad Universitaria, Ciudad Autónoma de Buenos Aires, C1428EHA, Argentina.
authors.forename: Daiana M
authors.initials: DM
authors.lastname: Vota
authors.forename: Renée L
authors.initials: RL
authors.lastname: Crisp
authors.forename: Alcira B
authors.initials: AB
authors.lastname: Nesse
authors.forename: Daniela C
authors.initials: DC
authors.lastname: Vittori
mesh_terms: D000328:Adult; D000535:Aluminum / Q000633:toxicity*; D000740:Anemia / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy; D001457:Anion Exchange Protein 1, Erythrocyte / Q000378:metabolism; D004905:Erythrocyte Aging / Q000187:drug effects / Q000502:physiology; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D004921:Erythropoietin / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008855:Microscopy, Electron, Scanning; D018384:Oxidative Stress / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: D001457:Anion Exchange Protein 1, Erythrocyte; C554270:EPO protein, human; D011994:Recombinant Proteins; D004921:Erythropoietin; D000535:Aluminum