Molecular Mechanism of Fluoride Induced Oxidative Stress and Its Possible Reversal by Chelation Therapy

Abstract

Fluorine (Fl) a member of the halogen family is the most electronegative and reactive of all the elements of the Periodic table. Chronic and acute exposures of fluoride leads to cardiovascular disease (hypertension and atherosclerosis), neurological disorders, gastrointestinal disturbances, liver disease, renal disease, reproductive effects, other health disorders and also affects the antioxidant system in the body. Furthermore, reactive oxygen species (ROS)-mediated oxidative damage is a common malady in fluoride pathogenesis. Formation of free radical due to cascade mechanism combined with glutathione-depleting agents increases the oxidation process in the cells and cause damage. Formation of ROS/RNS including peroxyl radicals (ROO•) the superoxide radical, singlet oxygen and hydroxyl radical (OH•) via the Fenton reaction direct DNA damages when both humans and animals are exposed to fluoride. In addition, fluoride induces the formation of oxidized lipids which in turn generate several bioactive molecules (ROS, peroxides and isoprostanes), of which aldehydes [malondialdehyde (MDA) and 4-hydroxy-nonenal (HNE)] are the major end products. Various synthetic antidotes were recommended for the present study such as DMSA (meso-2, 3-dimercaptosuccinic acid), and BAL (2, 3-dimercapto-1-propanol) for fluoride toxicity. However, it may cause side effect when used alone.  Recently, phyto-antidotes from plants or vegetables like flavonoid and polyphenols have played a major role in Fl induced oxidative stress-related diseases. In this thought, we included the various phytochemical used till now for mitigating fluoride-induced toxicity in different organs. Eventually, this review suggests that combination with natural and synthetic antidotes revealed a good strategy for chelating fluoride toxicity.

Keywords:  Toxicity, oxidative stress, glutathione (GSH), chelation therapy