Abstract
The excessive fluoride (F) exposure is associated with damage to cellular processes of different tissue types, due to changes in enzymatic metabolism and breakdown of redox balance. However, few studies evaluate doses of F compatible with human consumption. Thus, this study evaluated the effects of chronic exposure to sodium fluoride (NaF) on peripheral blood of mice from the evaluation of biochemical parameters. The animals were divided into three groups (n = 10) and received three concentrations of NaF in the drinking water for 60 days: mg/L F, 10 mg/L F, and 50 mg/L F. The blood was then collected for trolox equivalent antioxidant capacity (TEAC), thiobarbituric acid reactive substances (TBARS), concentrations of nitric oxide (NO), superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH). The results showed that doses of 10 mg/L F and 50 mg/L F were able to increase TBARS concentration and decrease NO levels and CAT activity in the blood, but there was no statistical difference for SOD levels. The 50 mg/L F group showed an increase in TEAC levels and a decrease in the GSH content when compared to the control group. In this way, oxidative changes in blood from chronic exposure to F, especially at the highest dose, indicate that F may be a toxic agent and, therefore, the long-term exposure to excessive doses should be avoided.
Excerpts:
The fluoride exposure doses used in our study (10 and 50 mg/L) are often employed [32–34] and lead to a plasma fluoride levels in rodents similar to the ones found in humans consuming artificially fluoridated water or living in areas of endemic fluorosis, respectively [35]. It is important to note that F metabolism in rodents is 5–10 times faster than that in humans and the concentrations used in this investigation, 10 and 50 mg/L, correspond to 1-2 and 5–10 mg/L, respectively, for humans in the drinking water [Dunipace et al., 1995].
… Fluoride, mainly in the form of hydrogen fluoride (HF), is transported through the cell membrane by nonionic diffusion [36]. The main mechanism of fluoride toxicity in cells is associated with its ability to interact with enzymes; most often, the fluoride can lead to inhibition of enzymatic activity (e.g., phosphatases, GTPases, and ATPases). In addition, fluoride can also inhibit the protein secretion and/or synthesis involved in signaling pathways (mitogen-activated protein kinase (MAPK), p53, activator protein-1 (AP-1), and nuclear factor kappa B (NF-?B) [37–39] and antioxidant enzymes (SOD, glutathione levels, and CAT) [40]. Thus, the inhibition of antioxidant enzymes results in the excessive production of ROS at the mitochondrial level, leading to cell damage. On the other hand, the fluoride at lower concentrations may stimulate enzymatic activity and promotes the increase of the cell proliferation and apoptosis because of the increase in proapoptotic proteins, such as caspase-3 and caspase-9 [41, 42]. Therefore, fluoride can also induce oxidative stress leading to the production of ROS, which triggers the release of cytochrome c from mitochondria into the cytosol and further activates caspase-3 leading to apoptotic cell death [41, 42].
*The full-text article is online at https://www.hindawi.com/journals/omcl/2018/8379123/
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