Fluoride exposure induces oxidative damage in primary astrocytes of SD rats and changes in the expression of α-synuclein and its effect on Nrf2-NQO1/HO-1 signaling pathway.

Long-term excessive fluoride intake accumulates in brain tissue, causing neuronal degeneration and nervous system dysfunction. This mechanism is closely related to elevated oxidative stress. α-Synuclein (α-Syn) is expressed in neuronal presynaptic terminals; under environmental toxin exposure or oxidative stress, its expression changes and it misfolds into oligomers and aggregates that are cytotoxic and induce oxidative cellular damage. Meanwhile, the nuclear factor erythroid 2-related factor 2 (Nrf2)-NAD(P)H: quinone oxidoreductase 1 (NQO1)/heme oxygenase-1 (HO-1) pathway is an important cellular system for regulating oxidative damage, and its core kinase is mainly expressed in brain astrocytes.The aim of this study is to investigate the effects of fluoride exposure on oxidative stress levels in astrocytes and the expression of α-Syn within the Nrf2-NQO1/HO-1 pathway. Primary astrocytes were treated with extracellular α-synuclein pre-formed fibrils (αSP) in conjunction with fluoride exposure. The results demonstrated that fluoride exposure induced reactive activation of primary astrocytes, increased levels of reactive oxygen species (ROS), decreased activities of superoxide dismutase (SOD) and catalase (CAT), and up-regulated the protein expression within the Nrf2-NQO1/HO-1 pathway. αSP caused oxidative stress in primary astrocytes and exacerbated oxidative damage induced by fluoride exposure. These findings are significant for enhancing the understanding of the mechanisms underlying brain injury associated with chronic fluorosis.