Abstract

Long-term excessive intake of fluoride (F) leads to chronic fluorosis, resulting in dental fluorosis and skeletal fluorosis. Chronic exposure to high doses of fluoride can also cause damage to soft tissues, especially when it passes through the blood-brain, blood-testis, and blood-placenta barrier, causing damage to the corresponding tissues. Fluorosis has become a public health problem in some countries or regions around the world. Understanding the pathogenesis of fluorosis is very important. Although the exact mechanism of fluorosis has not been fully elucidated, various mechanisms of fluoride-induced toxicity have been proposed. In this chapter, we will introduce the research progress of the mechanism of fluorosis, focusing on dental fluorosis, skeletal fluorosis, nervous and reproductive system toxicity, and influential factors related to fluoride toxicity (i.e., genetic background, co-exposure with other element). In addition, the application of proteomics and metabolomics in the study of the pathogenesis of fluorosis is also introduced. Currently, there is still no specific treatment for fluorosis. However, since fluorosis is caused by excessive intake of fluoride, avoiding excessive fluoride intake is the critical measure to prevent the disease. In endemic regions, health education and supplement diet with vitamins C, D and E, and calcium and antioxidant compounds are important.

Highlights

  • Chronic fluorosis is a systemic disease, high doses of fluoride leads to bioaccumulation in the body, especially hard tissues such as bones and teeth, and primarily harms bones and teeth [3–5]

  • The possible mechanisms involved different key proteins and signal transduction pathways associated with the pathogenesis of fluorosis have been proposed

  • Some high-throughput methods such as proteomics, metabolomics, and transcriptomics have been used in the study of the mechanism underlying development of fluorosis

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Summary

Introduction

Fluorine is a highly active gaseous element found widely in nature. Fluoride in small doses is beneficial for preventing dental caries and is commonly used in the prevention of dental caries [1, 2]. In China, fluorosis is caused by drinking water as well as inhaling combustion fumes of coal being used as an indoor fuel source [28–31]. Guizhou is one of the most severely afflicted areas of endemic fluorosis in China and this occurrence is due to indoor coal burning [30]. Another type of fluorosis is brick tea-type fluorosis, due to fluoride accumulation in brick tea. The underlying mechanisms of chronic fluorosis is still not well understood, the results of the previous studies indicated that fluoride can induce oxidative stress; regulate intracellular redox homeostasis; and lead to mitochondrial damage, endoplasmic reticulum stress, and alteration of gene expression [35–39]. This chapter reviews the present research on the potential adverse effects of overdose fluoride on various organisms, summarizes the molecular mechanism of fluorosis, and aims to improve our understanding of fluoride toxicity

Mechanisms of skeletal fluorosis
Nervous system toxicity
Reproductive system toxicity
Other systems
Genetic susceptibility to fluorosis
Co-exposure with other element
Proteomics and metabolomics applications
Method
Treatment and prevention of chronic fluorosis
Conclusions
Conflict of interest
Methods
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