Fluoride Binding Potential of Selected Phytochemicals: A Pilot Study.

Fluoride (F-) contamination in drinking water is a major global concern. According to several studies, India and China are the most affected by the presence of excess F-. Long-time exposure to F- concentrations above 1.5 ppm can lead to hard and soft tissue fluorosis (F- toxicity). There are no effective cure or treatment for fluorosis and the condition is almost irreversible. Considering water to be the prime media through which F- reaches humans, maintaining optimal F- levels in water remains the only possible remedy. F- endemic areas have adapted several conventional defluoridation techniques to resolve the issue. Among these, adsorption with plant compounds is widely used for F- removal. Studies have shown that plant metabolites can ameliorate the toxic effects of F-. Based on this, we attempt to elucidate the potential binding and electrochemical bio-sensing properties of selected phytochemicals towards F-. The focus of the present work is to evaluate the interactions of phytochemicals with F-; for which, the binding studies of phytochemicals with F- have been elaborated by UV-visible spectroscopy and emission techniques. Benesi-Hildebrand's (BH) plot was used to calculate the binding constant (CUR - 34.9 × 103 (M-1), QUER - 13 × 103 (M-1), ESC -6.3 × 103 (M-1), FIS - 5.36 × 103 (M-1) and PCA -1.5 × 103 (M-1), and detection limit (CUR - 1.54 × 10-7 M, QUER - 0.156 × 10-6 M, ESC - 0.221 × 10-6 M, FIS - 0.175 × 10-6 M, and PCA - 5.8 × 10-6 M) for the F-:phytochemical mixtures. Further, the binding characteristics were confirmed using 1H-NMR titration experiments. Our findings highlight the potential of phytochemicals as effective binding agents for F-, thereby reducing its bioavailability.

Fluoride Induced Neurobehavioral Impairments in Experimental Animals: a Brief Review.

Fluoride is one of the major toxicants in the environment and is often found in drinking water at higher concentrations. Living organisms including humans exposed to high fluoride levels are found to develop mild-to-severe detrimental pathological conditions called fluorosis. Fluoride can cross the hematoencephalic barrier and settle in various brain regions. This accumulation affects the structure and function of both the central and peripheral nervous systems. The neural ultrastructure damages are reflected in metabolic and cognitive activities. Hindrances in synaptic plasticity and signal transmission, early neuronal apoptosis, functional alterations of the intercellular signaling pathway components, improper protein synthesis, dyshomeostasis of the transcriptional and neurotrophic factors, oxidative stress, and inflammatory responses are accounted for the fluoride neurotoxicity. Fluoride causes a decline in brain functions that directly influence the overall quality of life in both humans and animals. Animal studies are widely used to explore the etiology of fluoride-induced neurotoxicity. A good number of these studies support a positive correlation between fluoride intake and toxicity phenotypes closely associated with neurotoxicity. However, the experimental dosages highly surpass the normal environmental concentrations and are difficult to compare with human exposures. The treatment procedures are highly dependent on the dosage, duration of exposure, sex, and age of specimens among other factors which make it difficult to arrive at general conclusions. Our review aims to explore fluoride-induced neuronal damage along with associated histopathological, behavioral, and cognitive effects in experimental models. Furthermore, the correlation of various molecular mechanisms upon fluoride intoxication and associated neurobehavioral deficits has been discussed. Since there is no well-established mechanism to prevent fluorosis, phytochemical-based alleviation of its characteristic indications has been proposed as a possible remedial measure.

Role of oxidative stress-mediated cell death and signaling pathways in experimental fluorosis.

Free radicals and other oxidants have enticed the interest of researchers in the fields of biology and medicine, owing to their role in several pathophysiological conditions, including fluorosis (Fluoride toxicity). Radical species affect cellular biomolecules such as nucleic acids, proteins, and lipids, resulting in oxidative stress. Reactive oxygen species-mediated oxidative stress is a common denominator in fluoride toxicity. Fluorosis is a global health concern caused by excessive fluoride consumption over time. Fluoride alters the cellular redox homeostasis, and its toxicity leads to the activation of cell death mechanisms like apoptosis, autophagy, and necroptosis. Even though a surfeit of signaling pathways is involved in fluorosis, their toxicity mechanisms are not fully understood. Thus, this review aims to understand the role of reactive species in fluoride toxicity with an outlook on the effects of fluoride in vitro and in vivo models. Also, we emphasized the signal transduction pathways and the mechanism of cell death implicated in fluoride-induced oxidative stress.