Peri-implant hypoxia as a potential barrier against ferroptotic mechanisms during peri-implant diseases: A cross-sectional study

Background: Hypoxia modulates inflammation and oxidative stress through hypoxia-inducible factor-1α (HIF-1α). Ferroptosis, an iron-dependent cell death process, is regulated by glutathione peroxidase-4 (GPX4) and involves lipid peroxidation markers like malondialdehyde (MDA). This study evaluates HIF-1α, GPX4, and MDA levels in peri-implant crevicular fluid (PICF) across peri-implant health, mucositis, and peri-implantitis. Methods: PICF samples were collected from 62 implants of 45 participants categorized into peri-implant health (PH), mucositis (PM), and peri-implantitis (PP) groups. Enzyme-linked immunosorbent assay (ELISA) quantified HIF-1α, GPX4, and MDA levels. Statistical analyses, including Kruskal-Wallis and Spearman correlation, assessed biomarker differences and associations. Results: Total MDA levels were significantly lower in PM and PP compared to PH (p = 0.014, p = 0.046). GPX4 levels were elevated in PM compared to PH (p = 0.034) but lower in PP than in PM (p < 0.001). While HIF-1α levels did not significantly differ among groups, their concentrations were notably higher in PH. A significant positive correlation was found between the total amounts of HIF-1α and GPX4 (r = 0.460, p < 0.01). Conclusion: Our findings demonstrated increased GPX4 and decreased MDA levels in peri-implant mucositis and peri-implantitis compared to peri-implant health, suggesting that ferroptosis may be inhibited in the peri-implant environment. Moreover, the positive correlation between HIF-1α and GPX4 levels indicates a potential regulatory role of hypoxia in modulating ferroptotic pathways in peri-implant tissues. Plain language summary: Bone loss around dental implants can lead to serious problems, putting the success of these implants at risk. Understanding how these issues develop is key to preventing and treating them. In the human body, cells can sometimes get damaged and die due to iron and stress caused by harmful molecules. This process, called “ferroptosis,” has recently gained attention in oral health research. Our study looked at whether low oxygen levels around dental implants might affect this process. We collected fluid samples from 45 people and measured 3 important substances linked to cell health and stress. We found that in diseased areas, the levels of molecules showing cell damage were lower, while the levels of substances that help protect cells were higher. This suggests that low oxygen conditions might actually help protect tissues around dental implants by preventing cell damage. These insights could help guide better ways to prevent and treat problems related to dental implants in the future.