Morphologic and functional alterations of erythroid cells induced by long-term ingestion of aluminium

Anaemia has been associated with aluminium (Al) accumulation in plasma and/ or bone tissue in patients with chronic renal insufficiency. Nevertheless, in previous works, we have found shortened red-cell life span, increased os motic resistance and inhibition of colony-forming units-erythroid (CFU-E) d evelopment in Al-overloaded rats with normal renal function. To elucidate f urther the action of Al on in vivo erythropoiesis, aluminium citrate was pr ovided to Sprague Dawley rats (n = 18) in the drinking water for 8 months. Significant decreases in haematocrit (38.8 +/- 4.29 versus 43.1 +/- 3.58%, p < 0.05) and blood haemoglobin concentration (137 +/- 10.1 versus 148 +/- 8.5 g/l, p < 0.05), reticulocytosis (1.8/1.3-4.2 versus 1.2/0.4-3.7%, p < 0 .05), and severe inhibition of CFU-E growth (670/120-950 versus 1530/810-24 40 CFLT-E/2 x 10(5) cells, p < 0.005) were found. Anysocytosis, poikilocyto sis and schistocytosis were detected in peripheral blood stained films. Sca nning electron microscopy revealed the presence of erythrocytes with abnorm al shape, including crenated and target cells. Aluminium was localised spec ially inside the schistocytes by EDAX analysis. Decreased haptoglobin conce ntration (107/83-127 versus 139/89-169 mg/l, p < 0.05) supports the assumpt ion of haemolytic nature of the anaemia. Rats were not iron depleted, as pl asma iron concentration and total iron binding capacity were found in the r ange of control values, and sideroblasts and haemosiderin deposits were obs erved in bone marrow smears. Total Fe-59 uptake and Fe-59 incorporated to h aem by the bone marrow cells were found decreased. In conclusion, the eryth ropoiesis impairment induced by Al may be a combined effect of direct actio n on circulating erythrocytes and interference with the cellular iron metab olism in erythroid progenitors. (C) 1999 Elsevier Science Inc. All rights r eserved.