Fluoride Action Network


1 Introduction

Given the widespread presence of fluorine in the natural environment, individuals are exposed to fluoride via food intake, inhalation, and dermal contact. Drinking water represents the largest exposure source. In particular, in highly fluoridated regions and in some developed areas that fluoridate the public water supply to reduce dental caries, fluoride may result in a health hazard [1,2].

Fluoride is required for normal growth and development of teeth and bones but can lead to fluorosis if taken excessively. Specifically, fluorosis can adversely affect the skeleton and teeth, and may induce structural and functional changes in soft tissues including brain tissue [3]. Epidemiological data show that chronic exposure to high fluoride in water is closely associated with a lower intelligence quotient in children [4,5,6]. In fluorosis-endemic areas, a certain high dose of fluoride intake is a potential risk factor for cognitive impairment in elderly people [7]. Moreover, structural changes in nerve cells and brain functions in experimental animals subjected to chronic fluorosis have been described such as nuclear shrinkage, mitochondrial swelling, neurodegeneration, and deterioration of learning and memory [8,9,10]. These findings suggest a direct link between excessive exposure to fluoride and brain function impairment, but little is known about mechanisms underlying these phenomena.

Oxidative stress-induced neurotoxicity is considered a mechanism of brain impairment caused by fluorosis. Once fluoride has formed lipid-soluble complexes in the blood, it can cross the blood–brain barrier, penetrate brain cells, and accumulate in brain tissue, causing detrimental neurological effects [11]. Reactive oxygen species (ROS) and free radicals can be generated when the fluoride content is high in the brain and cause oxidative damage and cell apoptosis in neurons [12], which may be controlled by apoptosis-related genes [13,14,15]. The literature suggests that increased ROS and lipid peroxidation (LPO) and decreased antioxidant enzyme activity occur in the brains of fluoride-intoxicated rats and that histopathological changes can be observed, especially swelling of mitochondria and endoplasmic reticulum dilation in neurons [9,16]. Also, some studies confirm that specific antioxidants may protect against this damage [17].

Anthocyanins, the largest group of water-soluble pigments responsible for fruit and vegetable color, are flavonoids reputed to have biological antioxidant activity due to their capacity as hydrogen donors [18]. They can also stabilize and delocalize unpaired electrons, and their ability to chelate transition metal ions may be useful [19]. Anthocyanin-rich maize purple plant pigment (MPPP) extracted from maize purple plant has been said to have antioxidant traits [3,20], but few reports of MPPP in fluoride-treated rat brains exist. Thus, we studied MPPP and any potential neuroprotective effects against fluoride toxicity.

3.1 Ultrastructural observation of brain

Ultrastructural analysis of the experimental rat brains is shown in Figure 2. For controls (Figure 2a), one oval nucleus with visible, clear nucleoli and double nuclear membranes, abundant mitochondria, and endoplasmic reticulum were found in neurons. In fluoride-treated rats (Figure 2b), nerves were deformed, lacked a nuclear membrane, and had chromatin condensation, swollen mitochondria, and broken cristae, and evidence of apoptosis was present. In rats treated with fluoride and MPPP, brain cells had swollen mitochondria but fewer abnormal mitochondria compared to group II, and pathological nuclear changes were reduced (Figure 2c and d).

5 Conclusions

Oxidative stress plays a role in fluoride-induced toxicity and provokes pathological changes and neuronal apoptosis in rat brains. Anthocyanin-rich MPPP may restore brain health via its antioxidant properties. However, further research is required to understand how MPPP may be neuroprotective.

*Full text article online at https://www.degruyter.com/view/journals/tnsci/11/1/article-p89.xml


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