Bhardwaj Nitin, Saxena Rajiv K
School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
School of Life Sciences, Jawaharlal Nehru University, New Delhi, India; Faculty of Life Sciences and Biotechnology, South Asian University, New Delhi, India.
PLoS One. 2014 Jun 19;9(6):e99364. doi: 10.1371/journal.pone.0099364. eCollection 2014.
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.
百草枯是一种广泛使用的除草剂，对人类和动物会产生多种毒性作用。本研究聚焦于百草枯与小鼠红细胞系统的相互作用。给C57Bl/6小鼠隔日腹腔注射百草枯（10毫克/千克体重），在第7、14和21天时间点导致血液红细胞计数显著下降，但到第28天红细胞计数恢复正常，表明对百草枯产生了耐受性。在接受百草枯处理的小鼠中观察到血液网织红细胞计数显著增加，到第28天也有所下降。在接受百草枯处理的小鼠中，循环中的年轻红细胞被随机从血液循环中清除，并且在该年龄组的红细胞中也观察到活性氧（ROS）水平显著升高。基于Ter119和转铁蛋白（CD71）受体的表达，通过流式细胞术鉴定并计数了骨髓和脾脏中代表红细胞分化各个阶段的细胞。在接受百草枯处理的小鼠骨髓中，红细胞的增殖活性、相对比例以及绝对数量均显著下降，但在接受百草枯处理的小鼠脾脏中，所有这些参数均显著升高。这些变化基本上局限于属于红细胞分化最早两个阶段的细胞。综合来看，我们的结果表明，百草枯处理导致小鼠出现短暂性贫血，这是由于年轻循环红细胞的随机清除以及骨髓中红细胞生成活性降低所致。然而，在接受百草枯处理的小鼠中，脾脏的红细胞生成活性有所升高。
