Oxidative stress due to aluminum exposure induces eryptosis which is prevented by erythropoietin.

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.

Differences in intramembrane particle distribution in young and old human erythrocytes.

The distribution of intramembrane particles in human erythrocytes was studied by freeze-fracture on young and old cells and compared to that obtained after ATP depletion or following addition of a clustering agent. It was shown that intramembrane particles became aggregated and the mean particle density increased as the cells aged. Likewise, both particle aggregation and increased density were found in young cells after moderate ATP depletion. In contrast, mean particle density was markedly reduced in both cell types after exhaustive depletion. Paradoxically, Zn treatment led to decreased particle density in young cells, whilst producing the opposite effect in aged cells. The results suggest that their low ATP content may account for the increased particle density of senescent cells.

Variation of micronucleated erythrocytes in peripheral blood of Sciurus aureogaster in relation to age: an increment of micronucleated polychromatic erythrocytes after the administration of colchicine.

In some species, in which the human is included, the influence of age in the variation in the number of micronucleated erythrocytes (MNE) is known. In the present work we show how the process of aging influences the number of spontaneous MNE in the gray squirrel (Sciurus aureogaster). Because of the difficulty of knowing the age of each animal, 69 animals were weighed at their arrival to the laboratory and at the start of sample taking, with the supposition that the heaviest animals were the oldest and those with the lightest weight were the youngest. The major number of MNE was found in the younger animals, whereas the adults displayed less MNE (P < 0.0001). A group of 11 animals were sampled every 15 days over a period of 6 months, and the number of MNE were found to decrease with an increment in the weight in conformity with the time elapsed. These results showed that in the gray squirrel, the number of spontaneous MNE in peripheral blood depend on age. An additional interesting datum about the increment of MNE after the administration of colchicine is shown.

Improved erythrocyte survival with combined vitamin E and selenium therapy in children with glucose-6-phosphate dehydrogenase deficiency and mild chronic hemolysis.

To study the antioxidant effect of high-dose vitamin E alone and in combination with selenium in patients with glucose-6-phosphate dehydrogenase deficiency with mild chronic hemolysis, 36 male children with such manifestations were enrolled consecutively into two equal groups. Group 1 received 800 IU vitamin E daily, and group 2 received 800 IU vitamin E in combination with 25 micrograms selenium. Hematologic status before and 2 months after treatment was evaluated. After treatment there was a significant change toward normal in both groups. The mean red cell half-life increased in group 1 from 16.9 to 22.8 days (P less than 0.01), and in group 2 from 15.6 to 24.3 days (P less than 0.01). A comparison of the mean difference of paired values in the two groups revealed a more significant increase in hemoglobin (0.9 +/- 0.1 gm/dl vs 1.2 +/- 0.2 gm/dl, P less than 0.05), hematocrit (2.4% +/- 0.4% vs 3.8% +/- 0.3%, P less than 0.05), and red cell half-life (5.9 +/- 3.0 days vs 9.1 +/- 4.4 days, P less than 0.01), and more significant reduction in reticulocytes (-0.7% +/- 0.2% vs -1.5% +/- 0.4%, P less than 0.01) in group 2. Clinical assessment and follow-up indicated no side effects related to the drugs.