CHANGES IN THE RAGE/NADPH OXIDASE SIGNALING PATHWAY AND OXIDATIVE STRESS LEVELS IN SH-SY5Y CELLS EXPOSED TO HIGH LEVELS OF FLUORIDE.

Excessive fluoride is known to induce oxidative stress and cell damage, particularly in the nervous system. We aimed to investigate changes in the expression of the receptor for advanced glycation end products (RAGE), p47phox, phosphop47phox, gp91phox, p22phox, and nuclear factor kappa B (NF-κB) in SH-SY5Y cells exposed to different levels of sodium fluoride and explore the molecular mechanisms underlying cell injury caused by excessive fluoride exposure. The cells were divided into the following groups: control, low-dose fluorinated (NaF 0.4 mmol/L), high-dose fluorinated (NaF 4 mmol/L), and FPS-ZM1 (1 µM). The protein levels of RAGE, p47phox, phospho-p47phox, gp91phox, p22phox, and NF-κB were detected using western blotting. Additionally, levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were detected using respective biochemical methods. Compared with those in the control group, the protein levels of RAGE, p47phox, phospho-p47phox, gp91phox, p22phox, and NF-κB were significantly upregulated in the high-dose fluorinated group (p<0.05). Moreover, compared with those in the high-dose fluorinated group, the protein levels of p47phox, phospho-p47phox, gp91phox, p22phox, and NF-κB were downregulated in the FPS-ZM1 group (p<0.05). Furthermore, compared with that in the control and high-dose fluorinated groups (p<0.05), the expression of SOD decreased in the high-dose fluorinated group and increased in the FPS-ZM1 group, respectively. Compared with that in the control group and high-dose fluorinated groups (p<0.05), MDA expression increased in the high-dose fluorinated group and reduced in the FPSZM1 group, respectively. Thus, excessive fluoride can upregulate the RAGE/NADPH oxidase signaling pathway in SH-SY5Y cells, and these changes may be related to the nerve cell injury caused by fluoride. [ABSTRACT FROM AUTHOR]