Preferential Elimination of Older Erythrocytes in Circulation and Depressed Bone Marrow Erythropoietic Activity Contribute to Cadmium Induced Anemia in Mice.

Sreoshi Chatterjee,Rajiv K Saxena,Eva Mezey

doi:10.1371/journal.pone.0132697

Sreoshi Chatterjee, Rajiv K Saxena + Show 1 more

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https://doi.org/10.1371/journal.pone.0132697

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Journal: PloS one	Publication Date: Jul 10, 2015
Citations: 14	License type: CC BY 4.0

Affiliation: Jawaharlal Nehru University, South Asian University

Abstract

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.

Highlights

Cadmium is one of the most toxic heavy metals, a common non-biodegradable environmental contaminant that causes serious health hazard [1,2,3,4]
Blood erythrocyte count and hemoglobin levels were monitored in control and cadmium exposed groups
Anemia as a consequence of cadmium toxicity has been observed in many cases of human exposure [22,23,24], and in animal models [25,26,27]

Summary

Introduction

Cadmium is one of the most toxic heavy metals, a common non-biodegradable environmental contaminant that causes serious health hazard [1,2,3,4]. A category I carcinogen [1], has a long biological half life (10–30 years), and it accumulates into various organs and tissues causing severe damage, in kidney [10,11,12] and in liver, lung, testis, bone, cardiovascular and the immune system [12,13]. Most severe example of cadmium toxicity was demonstrated by “itai-itai” (ouch-ouch) disease, endemic to the Jinzu river basin of Fuchu-Toyama Prefecture in Japan, characterized by osteomalacia and osteoporosis, renal tubular dysfunction, immune deficiencies and anemia [20,21,22]

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