Feeding
cadmium chloride (50 or 1000 ppm
CdCl2 in
drinking water, ad libitum) to C57BL/6 mice resulted in a significant and sustained fall in blood erythrocyte count and
hemoglobin levels that started 4 and 3 weeks after the start of 50 and 1000 ppm
cadmium doses respectively. A transient yet significant
reticulocytosis occurred during the first 4 weeks of
cadmium treatment. Using the recently developed double in vivo biotinylation (DIB) technique, turnover of erythrocyte cohorts of different age groups was simultaneously monitored in control and
cadmium treated mice. A significant accumulation of younger erythrocytes and a concomitant decline in the relative proportions of older erythrocytes in circulation was observed in both 50 and 1000 ppm
cadmium groups indicating that older erythrocytes were preferentially eliminated in
cadmium induced
anemia. A significant increase in the
erythropoietin levels in plasma was seen in mice exposed to 1000 ppm
cadmium. Levels of inflammatory
cytokines (IL1A,
IL6, TNFα, IFNγ) were however not significantly altered in
cadmium treated mice. A significant increase in cellular levels of
reactive oxygen species (ROS) was observed in older erythrocytes in circulation but not in younger erythrocytes. Erythropoietic activity in the bone marrows and spleens of
cadmium treated mice was examined by monitoring the relative proportion of cells belonging to the erythroid line of differentiation in these organs. Erythroid cells in bone marrow declined markedly (about 30%) in mice in the 1000 ppm
cadmium group but the decline was not significant in the 50 ppm
cadmium group. Cells representing various stages of erythroid differentiation in bone marrow and spleen were enumerated flow cytometrically by double staining with anti-Ter119 and anti-
transferrin receptor (CD71)
monoclonal antibodies. Decline of erythroid cells was essentially confined to pro-erythroblast and erythroblast-A, along with a concurrent increase in the splenic erythroid population indicating a stress response. In short
cadmium exposure causes preferential clearance of older erythrocytes from circulation along with a depressed erythropoietic activity at higher doses.