Rosangela M.M. Sawan, Giselle A.S. Leite, Maria C.P. Saraiva, Fernando Barbosa Jr., Jose E. Tanus-Santos, Raquel F. Gerlach. Fluoride increases lead concentrations in whole blood and in calcified tissues from lead-exposed rats. Toxicology, Volume 271, Issues 1–2, 30 April 2010, Pages 21–26.
Higher blood lead (BPb) levels have been reported in children living in communities that receive fluoride-treated water. Here, we examined whether fluoride co-administered with lead increases BPb and lead concentrations in calcified tissues in Wistar rats exposed to this metal from the beginning of gestation. We exposed female rats and their offspring to control water (Control Group), 100 mg/L of fluoride (F Group), 30 mg/L of lead (Pb Group), or 100 mg/L of fluoride and 30 mg/L of lead (F + Pb Group) from 1 week prior to mating until offspring was 81 days old. Blood and calcified tissues (enamel, dentine, and bone) were harvested at day 81 for lead and fluoride analyses. Higher BPb concentrations were found in the F + Pb Group compared with the Pb Group (76.7 ± 11.0 μg/dL vs. 22.6 ± 8.5 μg/dL, respectively; p < 0.001). Two- to threefold higher lead concentrations were found in the calcified tissues in the F + Pb Group compared with the Pb Group (all p < 0.001). Fluoride concentrations were similar in the F and in the F + Pb Groups. These findings show that fluoride consistently increases BPb and calcified tissues Pb concentrations in animals exposed to low levels of lead and suggest that a biological effect not yet recognized may underlie the epidemiological association between increased BPb lead levels in children living in water-fluoridated communities.
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Barbier, O., L. Arreola-Mendoza, and L.M. Del Razo. 2011 Molecular mechanisms of fluoride toxicity. Chem Biol Interact. 2010 Nov 5;188(2):319-33. Epub 2010 Aug 3.
Fig. 1. General scheme of the biological consequence of fluoride (F−) exposure on mammalian cells.
Abstract: Halfway through the twentieth century, fluoride piqued the interest of toxicologists due to its deleterious effects at high concentrations in human populations suffering from fluorosis and in in vivo experimental models. Until the 1990s, the toxicity of fluoride was largely ignored due to its “good reputation” for preventing caries via topical application and in dental toothpastes. However, in the last decade, interest in its undesirable effects has resurfaced due to the awareness that this element interacts with cellular systems even at low doses. In recent years, several investigations demonstrated that fluoride can induce oxidative stress and modulate intracellular redox homeostasis, lipid peroxidation and protein carbonyl content, as well as alter gene expression and cause apoptosis. Genes modulated by fluoride include those related to the stress response, metabolic enzymes, the cell cycle, cell-cell communications and signal transduction. The primary purpose of this review is to examine recent findings from our group and others that focus on the molecular mechanisms of the action of inorganic fluoride in several cellular processes with respect to potential physiological and toxicological implications. This review presents an overview of the current research on the molecular aspects of fluoride exposure with emphasis on biological targets and their possible mechanisms of involvement in fluoride cytotoxicity. The goal of this review is to enhance understanding of the mechanisms by which fluoride affects cells, with an emphasis on tissue-specific events in humans.
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