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.