Differential responses of neural-stem and kidney cells to sodium fluoride: insights into protein production, oxidative stress, and extracellular vesicle dynamics

Abstract Sodium fluoride (NaF) is a ubiquitous environmental pollutant that is widespread and has detrimental impacts on ecosystems and health. Developmentally, fluoride exposure enhances oxidative stress, including neurotoxicity and nephrotoxicity, and impacts fetal development. Several studies have shown that oxidative stress increases extracellular vesicle (EV) secretion. In this study, developmentally important human neural stem cells and embryonic kidney cells were used to evaluate the impact of various concentrations of NaF on the antioxidant status and EV production. Additionally, this study used vitamin C as an antioxidant to identify its benefits during developmental NaF exposure. This study revealed that human neural stem cells and embryonic kidney cells viability are affected by NaF exposure in a dose-dependent and temporal manner. Treatment with vitamin C increased the total antioxidant capacity but did not increase protein synthesis, as evaluated by measurements of total cellular protein content and cell viability in either cell type. Furthermore, compared with the control conditions, exposure to NaF reduced rather than increased extracellular vesicle production. Vitamin C treatment failed to modulate extracellular vesicle production in either cell line. This study revealed that reduced protein synthesis rather than reduced antioxidant activity is responsible for altered EV production and cell death upon exposure to NaF.