Using 8-Hydroxy-2'-Deoxiguanosine (8-OHdG) as a Reliable Biomarker for Assessing Periodontal Disease Associated with Diabetes

The paper introduces oxidative stress as a key driver of tissue damage through an imbalance between oxidants and antioxidants, contributing to DNA, lipid, and protein injury. Periodontitis is presented as a chronic inflammatory condition driven by dysbiotic biofilms and host immune responses, leading to destruction of periodontal tissues. Diabetes mellitus is highlighted as a major risk factor for periodontal disease, with bidirectional interactions mediated by inflammatory cytokines and reactive oxygen species (ROS). 8-OHdG, a stable product of oxidative DNA damage, is proposed as a biomarker to assess periodontal status, particularly in the context of diabetes-associated periodontitis. The research question/hypothesis centers on whether 8-OHdG can serve as a reliable biomarker for early detection, diagnosis, follow-up, and management of periodontal disease in diabetic patients to improve prognosis.

The review synthesizes evidence linking oxidative stress to both diabetes and periodontal disease, detailing mechanisms by which ROS produced by host immune cells (e.g., polymorphonuclear leukocytes) and periodontal pathogens contribute to tissue damage, collagen degradation, and potentially bone resorption. It summarizes multiple studies demonstrating elevated oxidative stress markers (e.g., superoxide dismutase, inducible nitric oxide synthase, malondialdehyde, reduced glutathione changes) in diabetic and/or periodontitis cohorts. The role of 8-OHdG across pathologies is covered: elevated levels in cardiovascular disease, stroke, chronic kidney disease, neurodegenerative disorders (Alzheimer’s, Huntington’s, Parkinson’s), various cancers (colorectal, ovarian), and aging. In periodontitis, salivary and gingival crevicular fluid 8-OHdG consistently increase, correlate with key pathogens (Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Treponema denticola, Tannerella forsythia), and decline after periodontal therapy. A meta-analysis reported higher salivary 8-OHdG in periodontal disease vs. healthy controls. The review also notes that systemic conditions (diabetes, obesity, hyperlipidemia) influence serum 8-OHdG, while local (salivary/gingival fluid) levels correspond more closely to periodontal status. Tables summarize study designs and outcomes, including cross-sectional and prospective works examining oxidative markers and 8-OHdG in saliva, gingival tissues, and serum.

Narrative review methodology: Two specialists independently searched PubMed and Web of Science using predefined keywords (8-hydroxy deoxy guanosine; oxidative stress; periodontitis; periodontal disease; diabetes mellitus; biomarkers). To reduce bias, both positive and negative papers on 8-OHdG effectiveness were considered, and only publications selected by both investigators were included. A total of 106 publications were selected for inclusion. Additionally, studies from the last 10 years (2014–2024) focusing on salivary 8-OHdG were identified (nine articles), largely using ELISA, with one study also measuring serum and one employing LC-MS/MS for higher sensitivity. No IRB or consent applicable due to review design.

- 8-OHdG is a robust marker of oxidative DNA damage and is elevated in inflammatory conditions, including periodontal disease and diabetes. - Diabetes–periodontitis interrelation: Poor metabolic control associates with higher oxidative stress and more severe periodontal lesions; systemic and local oxidative markers differ across groups. - Oxidative stress markers in oral context (Table 1 highlights): - Superoxide dismutase increased in gingival tissues of diabetic patients with chronic periodontitis (Akalın et al., 2008). - Inducible nitric oxide synthase elevated in diabetic and periodontitis patients (Jung et al., 2013). - Total antioxidant capacity lower in diabetic patients with periodontal disease (Pendyala et al., 2013; Vincent et al., 2018; Shashikumar et al., 2022). - Malondialdehyde higher and glutathione lower in diabetic tissues (Monea et al., 2014); salivary MDA increased with diabetes and TBSCH (Shee et al., 2020). - 8-isoprostane showed significant group differences; decreased in diabetic and periodontitis groups vs. controls (Koregol et al., 2018). - Scaling and root planing reduces GCF 8-OHdG and HbA1c in diabetic periodontitis patients (Muthuraj et al., 2017). - 8-OHdG and diabetes: - Serum and urinary 8-OHdG are elevated in T2DM; urinary 8-OHdG correlates positively with HbA1c (Negishi et al., 2001; Leinonen et al., 1997). - Elevated 8-OHdG in prediabetes and diabetes suggests early disease marker potential, outperforming some conventional markers (Al-Aubaidy & Jelinek, 2010). - Increased urinary 8-OHdG associates with diabetic nephropathy severity (Xu et al., 2004). - 8-OHdG and mtDNA deletion (4977 bp) serve as oxidative stress biomarkers in diabetics (Suzuki et al., 1999). - 8-OHdG and periodontitis: - Salivary 8-OHdG correlates with presence of periodontopathogens (e.g., Porphyromonas gingivalis) and decreases after periodontal therapy (Sugano et al., 2003; Sawamoto et al., 2005; Sezer et al., 2012; Yang et al., 2016). - Higher 8-OHdG in aggressive vs. chronic periodontitis; levels correlate with pocket depth (Grigorian et al., 2015) and nuclear anomalies/micronuclei in buccal cells (Zamora-Perez et al., 2015). - Population studies: Association between salivary 8-OHdG and severe periodontitis significant; odds ratios increased to OR 4.10 for drinking and OR 3.14 for smoking (Shin et al., 2016). - Clinical utility: LC-MS/MS detects lower 8-OHdG concentrations beyond ELISA range and correlates with ELISA values (Kurgan et al., 2015). 8-OHdG correlates with clinical parameters and is higher in chronic periodontitis vs. controls; decreases after therapy (multiple studies). - Meta-analysis and focused cohorts (Table 2): Salivary 8-OHdG is significantly higher in periodontitis (including diabetics), menopausal groups, and patients with acute coronary syndrome; provides strong investigative and prognostic potential for chronic periodontitis.

Findings support the hypothesis that 8-OHdG is a reliable biomarker for assessing periodontal disease, particularly in the context of diabetes. Elevated local (salivary, gingival crevicular fluid) 8-OHdG reflects periodontal oxidative stress and correlates with pathogen load, disease severity (pocket depth), and aggressive forms. Systemic 8-OHdG (serum/urine) tracks hyperglycemia and diabetic complications, linking metabolic control to periodontal outcomes. Reductions in 8-OHdG after periodontal therapy (e.g., scaling and root planing) and associations with total antioxidant capacity underscore its responsiveness to intervention and utility for monitoring. The bidirectional diabetes–periodontitis relationship mediated by ROS and inflammatory pathways highlights the biomarker’s relevance for integrated management: periodontal treatment may improve glycemic control, while optimizing diabetes management may attenuate periodontal oxidative damage. Collectively, evidence positions 8-OHdG as a practical, non-invasive marker to aid early detection, risk stratification, and therapeutic monitoring in periodontitis associated with diabetes.

8-OHdG is a pivotal, versatile biomarker of oxidative DNA damage with strong clinical relevance to periodontal disease and diabetes. The review consolidates mechanistic and clinical evidence that salivary and gingival crevicular fluid 8-OHdG levels rise with periodontal inflammation, correlate with key pathogens and disease severity, and decrease after therapy; systemic 8-OHdG aligns with hyperglycemia and diabetic complications. The integration of 8-OHdG into periodontal assessment, especially in diabetic patients, may enhance diagnosis, prognosis, and treatment monitoring, with potential benefits for glycemic control. Future research should focus on: larger, multicenter cohorts across diverse populations; longitudinal and interventional studies to validate clinical utility; standardization and clinical validation of assays (e.g., LC-MS/MS, next-generation sequencing, MALDI-TOF) for sensitivity and specificity; and incorporation into clinical guidelines for diabetes and periodontal care.

- Narrative review design without a predefined systematic protocol may introduce selection bias. - Inclusion limited to PubMed and Web of Science; potential database and publication bias. - Heterogeneity across studies in design (cross-sectional vs. prospective), populations, and assay methods (ELISA vs. LC-MS/MS), limiting direct comparability and meta-analytic synthesis beyond cited works. - Many studies are observational; confounding factors (smoking, drinking, metabolic control, comorbidities) may affect 8-OHdG levels. - Predominant focus on salivary measurements; fewer studies assess serum/urinary 8-OHdG in periodontal cohorts. - Need for more sensitive, specific, and clinically validated assays and broader geographic representation as noted by authors.