Excessive Fluoride Consumption Leads to Accelerated Death of Erythrocytes and Anemia in Rats
Excessive Fluoride Consumption Leads to Accelerated Death of Erythrocytes and Anemia in Rats
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DOI：
10.1007/s12011-013-9691-y
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发表时间：
2013-06-01
影响因子：
3.9
通讯作者：
Gusev, Gennadii Petrovich
中科院分区：
文献类型：
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作者：
Agalakova, Natalia Ivanovna;Gusev, Gennadii Petrovich
本研究旨在评价长期摄入过量氟(F)对大鼠红细胞的影响。这些动物被给予常规饮用水(0.4ppm F)或添加2，10和20ppm F(如NaF)的相同水12个月。长期暴露于氟剂量增加的大鼠可引起血浆氟浓度的进行性升高，并伴随着红细胞压积的剂量依赖性下降和平均红细胞体积的减少。摄入10ppm和20ppm氟可导致外周血中出现形态异常的细胞(口腔细胞和棘细胞)。水氟浓度升高到20ppmF时，暴露于磷脂酰丝氨酸的红细胞数量显著增加，但三组大鼠的细胞活力均受到抑制。网织红细胞的代偿性增强释放不足以补偿红细胞的损失。细胞内游离钙离子的剂量依赖性积累似乎是氟致大鼠红细胞死亡过程的主要病理生理过程。此外，10ppm和20ppm的氟可引起红细胞内ATP耗竭和过氧化产物的产生，而超氧化物和谷胱甘肽的水平没有改变。因此，长期中毒的氟大鼠由于固有的死亡相关的生化缺陷和贫血的发展而触发其红细胞的过早死亡。
The present study was performed to evaluate an overall effect of long-term consumption of excessive fluoride (F) amounts by rats on their erythrocytes. The animals were administered regular drinking water (0.4 ppm F) or the same water supplemented with 2, 10, and 20 ppm F (as NaF) for 12 months. Chronic exposure of the rats to increasing F doses induced a progressive rise of the plasma F concentration accompanied by a dose-dependent fall of hematocrit and decrease in the mean erythrocyte volume. Consumption of 10 and 20 ppm F resulted in appearance of morphologically abnormal cells (stomatocytes and echinocytes) in the peripheral blood. Rise of the water F concentration to 20 ppm F led to significant increase in the number of phosphatidylserine-exposing erythrocytes, although suppression of cell viability was revealed in all three groups of F-poisoned rats. A compensatory enhanced release of reticulocytes was not sufficient to compensate for erythrocyte loss. Dose-dependent accumulation of free cytosolic Ca2+ appears to be a major pathophysiological process underlying the development of F-induced death processes in rat erythrocytes. In addition, 10 and 20 ppm F induced ATP depletion and generation of peroxides in erythrocytes, whereas superoxide and glutathione levels were not altered. Thus, long-term intoxication of the rats with F triggers premature death of their erythrocytes due to intrinsic death-associated biochemical defects and development of anemia.