Analysis of HIF-1α, MDA, and GPX4 in Peri-Implant Crevicular Fluid

Completed

• Conditions: Peri-Implantitis and Peri-implant Mucositis; Hypoxia; Ferroptosis

• Registration Number: NCT06863116
• Lead Sponsor: Ege University

Brief Summary

Peri-implant diseases, such as peri-implant mucositis and peri-implantitis, are inflammatory conditions that affect the tissues surrounding dental implants. If untreated, these diseases can lead to bone loss and implant failure. This study investigates whether low oxygen levels (hypoxia) in the peri-implant environment influence ferroptosis, a type of cell death associated with oxidative stress. The research focuses on three key biomarkers: hypoxia-inducible factor-1 alpha (HIF-1α), glutathione peroxidase-4 (GPX-4), and malondialdehyde (MDA).

A total of 45 participants with 62 dental implants were included in the study. They were divided into three groups: peri-implant health, peri-implant mucositis, and peri-implantitis. Peri-implant crevicular fluid (PICF) samples were collected, and the levels of HIF-1α, GPX-4, and MDA were measured using laboratory tests.

The study aims to determine whether hypoxia affects ferroptosis-related pathways by altering GPX-4 and MDA levels. Understanding these mechanisms could provide new insights into peri-implant disease progression and help develop improved treatment strategies.

Detailed Description

Peri-implant diseases are characterized by an inflammatory response leading to progressive bone loss around dental implants. While microbial biofilms and host immune responses contribute to disease progression, recent studies have suggested that programmed cell death pathways, including ferroptosis, may also play a role. Ferroptosis is an iron-dependent form of non-apoptotic cell death that is regulated by GPX-4, a key enzyme that prevents lipid peroxidation, and MDA, a biomarker of oxidative damage. Hypoxia, a common feature in peri-implant disease, is known to modulate oxidative stress and inflammatory responses through HIF-1α, but its role in ferroptosis remains unclear.

This cross-sectional study aims to evaluate the relationship between hypoxia and ferroptosis in peri-implant diseases by measuring the levels of HIF-1α, GPX-4, and MDA in peri-implant crevicular fluid (PICF). A total of 45 participants with 62 dental implants were included in the study, categorized into peri-implant health (PH), peri-implant mucositis (PM), and peri-implantitis (PP) groups. PICF samples were collected using standardized paper strips, and biomarker levels were quantified via enzyme-linked immunosorbent assay (ELISA). Statistical analyses, including Kruskal-Wallis and Spearman correlation tests, were performed to assess differences among groups and potential associations between biomarkers.

The findings demonstrated that MDA levels were significantly lower in the peri-implantitis and peri-implant mucositis groups compared to peri-implant health, while GPX-4 levels were elevated in peri-implant mucositis and decreased in peri-implantitis. HIF-1α levels showed no significant differences among groups, but a positive correlation was observed between HIF-1α and GPX-4, suggesting a potential interaction between hypoxia and ferroptotic regulation in peri-implant tissues. These results imply that hypoxic conditions in peri-implant diseases may inhibit ferroptosis by modulating GPX-4 activity and reducing lipid peroxidation.

The study provides novel insights into the pathophysiology of peri-implant diseases, suggesting that the peri-implant microenvironment may exhibit unique regulatory mechanisms affecting ferroptotic pathways. While these findings contribute to our understanding of peri-implant disease pathogenesis, further longitudinal studies are needed to establish causal relationships and explore potential therapeutic strategies targeting hypoxia-ferroptosis interactions.

Study Timeline

• Study Start: 2023-05-15
• Primary Completion: 2024-05-15
• Study Completion: 2024-07-16
• Status Verified: 2025-03
• Study First Submitted: 2025-03-03
• Study First Submitted QC: 2025-03-03
• Last Update Submitted: 2025-03-03
• Study First Posted: 2025-03-07
• Last Update Posted: 2025-03-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 45

Inclusion Criteria

• Participants must have at least one dental implant functioning for a minimum of one year.
• No history of systemic diseases.
• No periodontal treatments (surgical or non-surgical) in the past six months.
• No use of antibiotics or other medications within the past six months.

Exclusion Criteria

• Systemic diseases, including but not limited to:

Diabetes mellitus Rheumatoid arthritis Cardiovascular disorders Immunological disorders Mucocutaneous diseases Contagious or communicable diseases

• Medication use, including:

Immunosuppressants Steroids Non-steroidal anti-inflammatory drugs (NSAIDs) Antiepileptics Calcium channel blockers Beta-blockers Anticoagulants Hormonal contraceptives Nutritional supplements

• Pregnant or lactating women.
• Use of orthodontic appliances or removable partial dentures.
• Poorly maintained implant-supported prostheses that may interfere with peri-implant crevicular fluid collection.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
HIF-1α, GPX-4, and MDA Levels in Peri-Implant Crevicular Fluid	Cross-sectional measurement at a single time point	Measurement of hypoxia-inducible factor-1 alpha (HIF-1α), glutathione peroxidase-4 (GPX-4), and malondialdehyde (MDA) levels in peri-implant crevicular fluid using enzyme-linked immunosorbent assay (ELISA) to assess their association with peri-implant health, mucositis, and peri-implantitis.

Trial Locations

Locations (1)

Ege University, Faculty of Dentistry, Department of Periodontology; 🇹🇷 İzmir, Turkey