Fluoride in the Central Nervous System and Its Potential Influence on the Development and Invasiveness of Brain Tumours—A Research Hypothesis

Abstract

The purpose of this review is to attempt to outline the potential role of fluoride in the pathogenesis of brain tumours, including glioblastoma (GBM). In this paper, we show for the first time that fluoride can potentially affect the generally accepted signalling pathways implicated in the formation and clinical course of GBM. Fluorine compounds easily cross the blood–brain barrier. Enhanced oxidative stress, disruption of multiple cellular pathways, and microglial activation are just a few examples of recent reports on the role of fluoride in the central nervous system (CNS). We sought to present the key mechanisms underlying the development and invasiveness of GBM, as well as evidence on the current state of knowledge about the pleiotropic, direct, or indirect involvement of fluoride in the regulation of these mechanisms in various tissues, including neural and tumour tissue. The effects of fluoride on the human body are still a matter of controversy. However, given the growing incidence of brain tumours, especially in children, and numerous reports on the effects of fluoride on the CNS, it is worth taking a closer look at these mechanisms in the context of brain tumours, including gliomas.

Ameliorative Potential of Ginger (Zingiber officinale) following Repeated Coexposure with Fluoride and Dimethoate in Blood and Brain of Wistar Rats

“…Evidence is emerging that rising levels of environmental degradation and omnipresent pollution are major incriminating factors for the signifcant spurt in cases of mental health diseases around the world [55]. Since inherent high lipid concentration in nervous tissue makes it especially susceptible to oxidant damage, pollutants, such as F and OP pesticides such as DM which can cross the blood-brain barrier, may induce oxidative brain injury and neuroinfammation [29,56,57]. Erythrocytes transport gases and maintain systemic redox equilibrium but are among the frst to bear the brunt of oxidative damage in the event of excessive generation of reactive oxygen species owing to exposure to environmental pollutants, which not only damages their structure and reduces their fnite lifespan but also can impinge systemic oxygen delivery causing anemia and hypoxia [58,59].…”

“…Skeletal fuorosis can occur after an intake of 6-10 mg of F per day for at least 10 days [20]. Apart from skeletal deformities, such as arthritis and osteoporosis, fuorosis also predisposes to neurological developmental disabilities and heightens the risk of formation of certain brain tumors as it can readily permeate the bloodbrain barrier [27][28][29]. Intellectual impediments in humans, such as impaired memory, slow learning ability, and low intelligence quotients, have been reported in areas where the groundwater carries high F content [30].…”

Dual-Responsive Near-Infrared BODIPY-Based Fluorescent Probe for the Detection of F– and HClO in Organisms

“…For example, excessive F – can lead to increased renal oxidative stress, affecting kidney function through the ROS-mediated SIRT3 signaling pathway . Neuronal damage from high fluoride exposure correlates with cellular oxidative stress and inflammation . Moreover, increased ROS levels have been noted in conditions like skeletal fluorosis, liver damage, and cardiovascular diseases caused by excessive intake of F – . − Some studies imply there is a potential link and the physiological relevance between F – and HClO.…”

Evaluation of Ilex guayusa and Piper marginatum Extract Cytotoxicity on Human Dental Pulp Mesenchymal Stem Cells

“…In preventive and conservative treatments, fluoride is used as a reference mineral, as it strengthens tooth enamel and helps prevent dental caries [ 9 ]. However, excessive fluoride consumption can cause health problems [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ]. Fluoride toxicity usually occurs when extreme amounts of fluoride are ingested through drinking water [ 19 , 21 ], fluoride supplements [ 30 , 31 ], toothpaste [ 32 ], or in extreme cases, by ingesting products such as pesticides or insecticides that contain fluoride [ 33 ].…”

“…In addition to dental fluorosis, chronic exposure to high levels of fluoride can cause other adverse health effects [ 15 , 16 , 17 , 18 , 23 , 31 ], such as generating bone problems [ 15 ], causing liver and kidney damage [ 16 ], affecting the gastrointestinal system [ 40 ], and inducing neurological disorders [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 31 , 32 , 34 , 35 ].…”