Management strategies for fluoride toxicity and the critical role of epigenetic therapy

Fluoride is an essential trace element primarily known for its role in preventing dental caries; however, excessive exposure can lead to adverse health effects. Emerging research suggests possible links between fluorosis and neurodevelopmental disorders, including reduced cognitive function and increased prevalence of ADHD. Its impact on liver health such as hepatotoxicity and hormone-related infertility also raises concern. Moreover, high fluoride exposure has been associated with various toxicities, including skeletal fluorosis, reproductive toxicity, and neurotoxicity, potentially driven by mechanisms involving oxidative stress and DNA damage. Recent studies have emphasized the critical role of epigenetic mechanisms in mediating fluoride's toxic effects. Epigenetics refers to stable yet reversible changes in gene expression that do not involve alterations in the DNA sequence, such as DNA methylation, histone modifications, and non-coding RNA regulation. Fluoride toxicity can disrupt normal methylation patterns and induce histone modifications, leading to abnormal expression of genes involved in apoptosis, oxidative stress, and inflammatory pathways. Additionally, microRNAs have been implicated in fluoride-induced reproductive dysfunction and neurotoxicity. In this review article, we provide a comprehensive overview of the evidence on the mechanism of fluoride-induced fluorosis, reproductive toxicity, and neurological impairment. We elaborate on current and future treatments, highlighting promising epigenetic drug candidates for managing fluoride toxicity. Understanding the epigenetic landscape of fluoride toxicity opens new avenues for therapeutic interventions, primarily targeting DNA methylation and histone modification pathways to mitigate its adverse health effects.