Abstract
This study investigated the effects of fluoride exposure on the mRNA expression of Cav1.2 calcium signaling pathway and apoptosis regulatory molecules in PC12 cells. The viability of PC12 cell receiving high fluoride (5.0mM) and low fluoride (0.5mM) alone or fluoride combined with L-type calcium channel (LTCC) agonist/inhibitor (5umol/L FPL6417/2umol/L nifedipine) was detected using cell counting kit-8 at different time points (2, 4, 6, 8, 12, 10, and 24h). Changes in the cell configuration were observed after exposing the cells to fluoride for 24h. The expression levels of molecules related to the LTCC were examined, particularly, Cav1.2, c-fos, CAMK II, Bax, and Bcl-2. Fluoride poisoning induced severe cell injuries, such as decreased PC12 cell activity, enhanced cell apoptosis, high c-fos, CAMKII, and Bax mRNA expression levels. Bcl-2 expression level was also reduced. Meanwhile, high fluoride, high fluoride with FPL64176, and low fluoride with FPL64176 enhanced the Cav1.2 expression level. In contrast, low fluoride, high fluoride with nifedipine, and low fluoride with nifedipine reduced the Cav1.2 expression level. Thus, Cav1.2 may be an important molecular target for the fluorosis treatment, and the LTCC inhibitor nifedipine may be an effective drug for fluorosis.
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Excessive ER stress and the resulting autophagic flux dysfunction contribute to fluoride-induced neurotoxicity.
Highlights Excessive ER stress plays an important role in NaF-induced neurotoxicity. NaF-induced neuronal death is caused by ER stress-elicited apoptosis and the impaired autophagic flux. Impaired autophagic flux was mediated by excessive ER stress in NaF-induced neurotoxicity. Fluoride is capable of inducing neurotoxicity, but its mechanisms remain elusive. This study
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Rutin attenuates neurobehavioral deficits, oxidative stress, neuro-inflammation and apoptosis in fluoride treated rats.
Highlights The influence of rutin on fluoride – induced neurotoxicity in rat was studied. Rutin reversed the fluoride – induced neurobehavioral deficits in rats. Rutin reversed the fluoride – induced inhibition of acetylcholinesterase activity in rat cerebrum and striatum. Rutin enhanced antioxidant status and inhibited neuro-inflammation and apoptosis in fluoride
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Challenges of fluoride pollution in environment: Mechanisms and pathological significance of toxicity – A review.
Highlights Fluoride exposure induces mitochondrial function dysfunction. Fluoride exposure mediates organs injury involved in apoptosis and autophagy. Fluoride exposure induces inflammatory reaction. Fluoride exposure results changes in intestinal microbial abundance. Fluoride is an important trace element in the living body. A suitable amount of fluoride has a beneficial effect on
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Protective effects of vitamin C against fluoride toxicity.
Fluorine is a highly toxic substance that is widely distributed with drinking water and nutrients. While fluorine is not free in nature, it can form compounds with almost all metals and nonmetals except oxygen and inert gases. Fluorine is found in the environment in water, soil, air, nutrients, and vegetation
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Impaired V-ATPase leads to increased lysosomal pH, results in disrupted lysosomal degradation and autophagic flux blockage, contributes to fluoride-induced developmental neurotoxicity.
Highlights NaF exposure caused developmental neurotoxicity. NaF-induced neuronal apoptosis results from autophagic flux blockage. Raised lysosomal pH disrupting lysosomal degradation caused autophagic flux blockage. V-ATPase is a crucial factor regulating neuronal lysosomal pH. Upregulation of V-ATPase alleviate NaF-induced developmental neurotoxicity. Fluoride is capable of inducing developmental neurotoxicity, yet its mechanisms
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Fluoride's Direct Effects on Brain: Animal Studies
The possibility that fluoride ingestion may impair intelligence and other indices of neurological function is supported by a vast body of animal research, including over 40 studies that have investigated fluoride's effects on brain quality in animals. As discussed by the National Research Council, the studies have consistently demonstrated that fluoride, at widely varying concentrations, is toxic to the brain.
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Fluoride's Effect on Fetal Brain
The human placenta does not prevent the passage of fluoride from a pregnant mother's bloodstream to the fetus. As a result, a fetus can be harmed by fluoride ingested pregnancy. Based on research from China, the fetal brain is one of the organs susceptible to fluoride poisoning. As highlighted by the excerpts
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Fluoride & IQ: 76 Studies
Note: See the Updated list of fluoride IQ studies at https://fluoridealert.org/researchers/fluoride-iq-studies/the-fluoride-iq-studies/ • As of July 18, 2022, a total of 85 human studies have investigated the relationship between fluoride and human intelligence. • Of these investigations, 76 studies have reported that elevated fluoride exposure is associated with reduced IQ in humans. • The studies
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Fluoride Affects Learning & Memory in Animals
An association between elevated fluoride exposure and reduced intelligence has now been observed in 65 IQ studies. Although a link between fluoride and intelligence might initially seem surprising or random, it is actually consistent with a large body of animal research. This animal research includes the following 45 studies (out
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Fluoride: Developmental Neurotoxicity.
Developmental Neurotoxicity There has been a tremendous amount of research done on the association of exposure to fluoride with developmental neurotoxicity. There are 78 studies reporting reduced IQ (75 studies with children and 3 studies with adults) and several on the impaired learning/memory in animals. And there are studies which link
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