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. 2025 Aug;203(8):4118-4127.
doi: 10.1007/s12011-024-04499-5. Epub 2025 Jan 4.

Fluoride Induces Toxic Effects on the A549 Pulmonary Cell Line at Non-cytotoxic Concentrations

Affiliations

Fluoride Induces Toxic Effects on the A549 Pulmonary Cell Line at Non-cytotoxic Concentrations

Sánchez-Gasca J E et al. Biol Trace Elem Res. 2025 Aug.

Abstract

Fluoride is emitted into the air not only through gas emissions but also from volcanic ash, leading to contact via inhalation. Therefore, the objective of the present study was to evaluate the cellular and biochemical responses in the A549 cell line after exposure to NaF (sodium fluoride) concentrations lower than those previously used in other studies to determine the impact on the lung epithelium. A549 cells were exposed to different concentrations (0.0001 to 5 mM) of NaF for 24 h. No cytotoxicity was observed in the cells after exposure to NaF concentrations of 0.0001 to 1 mM. However, an increase in oxidative damage was observed at concentrations of 0.0001-0.001 and 1-5 mM. There were alterations in the antioxidant system related to glutathione synthesis, since there was a decrease in glutathione-s-transferase activity and γ-glutamyltransferase concentration at non-cytotoxic concentrations. Non-cytotoxic concentrations also resulted in an increase in the expression of the proteins pulmonary surfactant B and γ-glutamyl cysteine ligase. A reduction in PPARα was also observed, which coincided with a decrease in the levels of non-esterified fatty acids at the same NaF concentrations. Finally, IL-6 was the only interleukin with increased levels at all NaF concentrations. In general, an increase was also observed in the other interleukins, but only at concentrations of 0.1-5 mM. These results suggest that the lung epithelium may be a toxicological target of fluoride after exposure to low concentrations.

Keywords: Cytotoxicity; Fluoride toxicity; Oxidative stress; Sodium fluoride.

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Conflict of interest statement

Declarations. Competing Interests: The authors declare no competing interests.

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