Abstract
Paraquat a widely used herbicide causes a variety of toxic effects on humans and animals. The present study is focused on the interaction of paraquat with the mouse erythroid system. Administration of paraquat (10 mg/kg body weight i.p. on alternate days in C57Bl/6 mice) induced a significant fall in blood erythrocyte count on 7, 14, and 21 day time points but the erythrocyte count reverted back to normal by 28th day indicating the emergence of refractoriness to paraquat. A marked surge in the blood reticulocyte count was observed in paraquat treated mice that also subsided by 28th day. Young erythrocytes in circulation were randomly eliminated from blood circulation in paraquat treated mice and a significant elevation in the level of reactive oxygen species (ROS) was also observed maximally the erythrocytes of this age group. Cells representing various stages of erythroid differentiation in bone marrow and spleen were identified and enumerated flow cytometrically based on their expression of Ter119 and transferrin (CD71) receptor. Proliferative activity of erythroid cells, their relative proportion as well as their absolute numbers fell significantly in bone marrow of paraquat treated mice but all these parameters were significantly elevated in spleens of paraquat treated mice. These changes were essentially restricted to the cells belonging to the two earliest stages of erythroid differentiation. Taken together our results indicate that paraquat treatment causes a transient anemia in mice resulting from random elimination of young circulating erythrocytes as well as depressed erythropoietic activity in bone marrow. Spleen erythropoietic activity however was elevated in paraquat treated mice.
Highlights
Paraquat (N, N’-dimethyl-4,49-bipyridinium dichloride) was first synthesized in 1880 but its action as a potent herbicide was discovered only in 1955 [1]
These results show that paraquat treatment induced a transient anemia in mice that is associated with a surge of reticulocytes representing enhanced erythropoietic activity
From 12 to 40 days of age, erythrocytes are lost at an average rate of 1.3% per day and the rate of loss further increases to 2.8% from 40 to 60 days of age, by which time point virtually all erythrocytes of the cohort are lost from the circulation [24]
Summary
Paraquat (N, N’-dimethyl-4,49-bipyridinium dichloride) was first synthesized in 1880 but its action as a potent herbicide was discovered only in 1955 [1]. This compound soon became one of the most widely used herbicide in crop management. Long-term exposures to paraquat causes lung and eye damage though reproductive/fertility damage was not found by the United States Environmental Protection Agency [6]. Paraquat is a potent inducer of reactive oxygen species (ROS) and occurrence of anemia as a consequence of exposure to paraquat has been documented [9,10]. Attendant changes in erythropoietic activity in bone marrow and spleen were examined
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