Excessive Fluoride Consumption Leads to Accelerated Death of Erythrocytes and Anemia in Rats
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Excessive Fluoride Consumption Leads to Accelerated Death of Erythrocytes and Anemia in Rats Natalia Ivanovna Agalakova & Gennadii Petrovich Gusev
Received: 14 February 2013 / Accepted: 30 April 2013 / Published online: 15 May 2013 # Springer Science+Business Media New York 2013
Abstract 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. Keywords Rat erythrocytes . Fluoride . Premature death . Anemia . Reticulocyte production . Intracellular calcium
N. I. Agalakova (*) : G. P. Gusev Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 44 M. Thorez pr., Saint Petersburg 194223, Russia e-mail: [email protected]
Introduction Fluoride (F) is a common therapeutic agent used for health improvement of the teeth and bones by means of water fluoridation, F-containing dental products and food supplements. Public health officials consider water fluoridation as one of the ten greatest achievements of the twentieth century in disease prevention along with purification of drinking water, pasteurization of food products, and immunization against infectious diseases. However, presently there are no convincing proofs on the necessity of F for normal human growth and development. In contrast, numerous investigations have established various harmful effects of F on the living organisms. In many parts of the world, consumption of water with high F content leads to development of fluorosis, a slow degenerative disease associated with alterations in the teeth and bones, neurological defects, infertility, and mental retardation [1–3]. In developed countries, uncontrolled use of fluoridated wate
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