Chronic Exposure to Fluoride Affects GSH Level and NOX4 Expression in Rat Model of This Element of Neurotoxicity

Abstract

Exposure of neural cells to harmful and toxic factors promotes oxidative stress, resulting in disorders of metabolism, cell differentiation, and maturation. The study examined the brains of rats pre- and postnatally exposed to sodium fluoride (NaF 50 mg/L) and activity of NADPH oxidase 4 (NOX4), catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), concentration of glutathione (GSH), and total antioxidant capacity (TAC) in the cerebellum, prefrontal cortex, hippocampus, and striatum were measured. Additionally, NOX4 expression was determined by qRT–PCR. Rats exposed to fluorides (F-) showed an increase in NOX4 activity in the cerebellum and hippocampus, a decrease in its activity in the prefrontal cortex and hippocampus, and upregulation of NOX4 expression in hippocampus and its downregulation in other brain structures. Analysis also showed significant changes in the activity of all antioxidant enzymes and a decrease in TAC in brain structures. NOX4 induction and decreased antioxidant activity in central nervous system (CNS) cells may be central mechanisms of fluoride neurotoxicity. NOX4 contributes to blood–brain barrier damage, microglial activation, and neuronal loss, leading to impairment of brain function. Fluoride-induced oxidative stress involves increased reactive oxygen speciaes (ROS) production, which in turn increases the expression of genes encoding pro-inflammatory cytokines.