Antimony Exposure Promotes Periodontitis by Activating Ferroptosis Pathway

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BACKGROUND: Growing evidence indicates a correlation between heavy metal exposure and various diseases. However, studies examining the impact of heavy metal exposure on periodontitis remain limited. The research investigated potential links between heavy metal exposure and periodontal disease development. METHODS: Using the 2009-2014 NHANES, we employed generalized additive models (GAM), multivariate logistic regression, quartile logistic regression, weighted quantile sum (WQS) regression, and subgroup analysis to investigate the association between heavy metal exposure and periodontitis. Mechanisms of antimony's effects were identified by GO/KEGG analysis combined with experimental validation. RESULTS: Lead and antimony showed significant dose-response relationships with periodontitis. The subgroup analysis revealed more pronounced effects among female participants compared to males, and individuals under 60 years had a higher number of significant associations than those over 60. WQS regression indicated that antimony contributed most to periodontitis among mixed heavy metal exposures. GO/KEGG enrichment analysis suggested that antimony exacerbates periodontitis via the ferroptosis pathway. CONCLUSION: Exposure to heavy metals, particularly lead and antimony, is associated with elevated risks of periodontitis, with significant effect modification by gender and age. Based on these results, antimony was further investigated and found to exacerbate inflammation via ferroptosis, as confirmed experimentally.

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