# Fluoride and Pineal Gland
## 4 Fluoride Accumulation in the Pineal Gland and Its Consequences
The authors [11] were of the opinion that fluoride exposure may contribute to increased pineal gland calcification and subsequent decreases in nighttime melatonin production that contribute to sleep disturbances. For obvious reasons, there are very few reports on the accumulation of fluoride in the pineal gland and its effect on the functionality of the organ in humans. Therefore, it is worth noting the studies carried out in both experimental and free-living animals. In the pineal glands taken from the common merganser (_Mergus merganser_), [PERSON] et al. [1] recorded very high fluoride contents (mean > 1000 mg/kg dw), which even exceed the concentrations observed in the bones of these birds. Such a high concentration of fluoride in the gland is explained by the incompleteness of the blood-brain barrier in birds, which facilitates the penetration of various substances into the central nervous system. [PERSON] and [PERSON] [79] conducted a study to determine the effect of fluoride removal from the diet of aged rats (over 26 months of age) on the pineal cell structure and to compare the results with rats receiving fluoride with food (control). It was observed that in animals deprived of fluoride for 8 weeks, the number of pinealocytes was higher than in control animals, which suggests a harmful effect of fluoride contained in the diet on pineal morphology and thus on the production and secretion of melatonin. In turn, studies conducted by [PERSON] and [PERSON] [106; 107] in rats showed the beneficial effect of melatonin and pineal proteins on fluoride-induced oxidative stress, which is one of the best known effects of fluoride on the body [108; 109]. The animals were exposed to different doses of fluoride and melatonin and proteins obtained from buffalo pineal (_Bubalus bubalis_). The severity of oxidative stress was measured by the degree of activity of antioxidative enzymes: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), as well as the concentration of reduced glutathione (GSH) and malondialdehydedehyde (MDA) in the brains of the animals [6]. The antioxidant system parameters were markedly improved by the intake of melatonin and pineal proteins; in the latter case, the beneficial effect was even stronger. The action consisted of increased activity of antioxidant enzymes, increased GSH concentration, and decreased MDA concentration. All these parameters were adversely affected in the group of animals receiving fluoride only (decreased activity of enzymes and GSH concentration and increased MDA concentration, which is a marker of increased oxidative stress), painting a very disturbing picture of the effects of fluoride accumulation in the pineal gland. Since it is known that fluoride reduces the production and secretion of melatonin [79], a substance which reduces the oxidative stress induced by them [107], the accumulation of fluoride in the pineal gland may be a significant factor in enhancing the effects of reactive oxygen species, with all potential adverse consequences. Finally, it is worth mentioning that the concentrations of fluoride in the pineal gland at the magnitude of several dozen or even several hundred mg/kg ww, revealed in the studies by [PERSON] [52] and [PERSON] et al. [53], may show inhibitory activity on melatonin synthesis pathway enzymes. Fluoride having this effect has been known for a long time in relation to many enzymes [108; 110]. Thus, it cannot be excluded that the restriction of melatonin synthesis associated with pinealocyte calcification may be caused not only by a decrease in the number of active pinealocytes but also by the direct influence of fluoride accumulated in the gland on enzymatic activity. This issue undoubtedly needs to be clarified in the future. **Funding:** This research received no external funding. **Conflicts of Interest:** The authors declare no conflict of interest.