Fluoride Metabolism and Toxicity Assessment in Biological Systems

Fluoride is a ubiquitous element encountered through water, food and ambient air, and its systemic journey encompasses absorption, distribution, metabolism and excretion. Following ingestion, fluoride is rapidly absorbed in the stomach and small intestine, after which it distributes predominantly to mineralising tissues such as bone and teeth, but also to soft tissues. Metabolic handling involves renal excretion, with clearance rates influenced by factors including pH, ionic competition and individual physiology. At low concentrations, fluoride contributes to enamel remineralisation and caries prevention; however, chronic or high-dose exposure can disrupt cellular homeostasis. Toxic effects manifest in diverse systems: skeletal fluorosis arises from cumulative bone deposition, characterised by altered osteoblast and osteoclast function; neurotoxicity may occur through perturbation of neurotransmitter synthesis and oxidative balance in the central nervous system; gastrointestinal toxicity entails enteric nervous system disruption and proteomic remodelling of intestinal tissues. Assessment of fluoride toxicity integrates analytical chemistry to quantify systemic levels, proteomic and biochemical assays to detect molecular perturbations, and functional tests ranging from cellular bioenergetics to animal behaviour. A multidisciplinary approach is essential to delineate safe exposure thresholds, identify susceptible populations and develop mitigation strategies that balance caries control with systemic health.

Research from Nature Portfolio

Recent studies have applied advanced proteomic and morphological analyses to elucidate the impact of chronic fluoride exposure on the small intestine. Investigations in rodent models revealed dose-dependent alterations in the density of myenteric plexus neurons and changes in neurochemical varicosities, alongside shifts in proteins governing glucose homeostasis and protein synthesis within the jejunum. Complementary work in the duodenum demonstrated morphological remodelling of enteric neurons and modulation of cytoskeletal and metabolic proteins under prolonged fluoride intake. An additional investigation into physically active, fluorosis-susceptible mice showed that chronic exercise did not significantly influence plasma or bone fluoride levels, although high fluoride exposure correlated with reduced body weight and diminished exercise performance, indicating a complex interplay between physical activity and fluoride kinetics.

Fluoride Metabolism and Toxicity Assessment in Biological Systems publication trend

The graph below shows the total number of articles in fluoride metabolism and toxicity assessment in biological systems across all publications each year (not limited to Nature Index journals).

Technical terms

Proteomics: High-throughput analysis of proteins expressed in a biological sample.

Enteric nervous system: Intrinsic neuronal network of the gastrointestinal tract that controls motility and secretion.

Oxidative stress: Cellular condition in which an excess of reactive oxygen species overwhelms antioxidant defences.

Glycogen metabolism: Series of enzymatic reactions regulating the synthesis and breakdown of glycogen.

Myenteric plexus: Layer of neurons between the muscle layers of the gastrointestinal wall responsible for coordinating peristalsis.

References

1. Chronic treatment with fluoride affects the jejunum: insights from proteomics and enteric innervation analysis. Scientific Reports (2018).
2. Enteric innervation combined with proteomics for the evaluation of the effects of chronic fluoride exposure on the duodenum of rats. Scientific Reports (2017).
3. Effect of chronic exercise on fluoride metabolism in fluorosis-susceptible mice exposed to high fluoride. Scientific Reports (2018).
4. Fluoride as a Potential Repressor of Glycogen Metabolism in Skeletal Muscle Cell Line CCL136. Molecules (2023).
5. Effects of Fluoride Long-Term Exposure over the Cerebellum: Global Proteomic Profile, Oxidative Biochemistry, Cell Density, and Motor Behavior Evaluation. International Journal of Molecular Sciences (2020).
6. Effects of Fluoride on Submandibular Glands of Mice: Changes in Oxidative Biochemistry, Proteomic Profile, and Genotoxicity. Frontiers in Pharmacology (2021).