Interaction of Hypoxia and Kynurenine Pathway in Periodontal Inflammation

Abstract

The kynurenine pathway (KP), the primary route of tryptophan (TRP) metabolism, is influenced by inflammation and hypoxia and has been linked to immune dysregulation and oxidative stress. This study investigated the relationship between KP activity and hypoxia in periodontal inflammation, as well as their association with clinical periodontal parameters. A total of 23 systemically healthy patients with stage III, grade B periodontitis and 22 periodontally healthy individuals were included. Salivary and serum levels of tumor necrosis factor-alpha (TNF-alpha), hypoxia-inducible factor-1 alpha (HIF-1 alpha), and 8-hydroxy-2 '-deoxyguanosine (8-OHdG) were measured using ELISA. KP metabolites were analyzed via liquid chromatography-mass spectrometry. Results showed that salivary TNF-alpha, HIF-1 alpha, and 8-OHdG levels were significantly higher in the periodontitis group (P < .05). Both salivary and serum kynurenine/tryptophan (KYN/TRP) ratios and picolinic acid (PA), along with salivary 3-hydroxykynurenine (3OHKYN) and serum kynurenine (KYN), were elevated in periodontitis (P < .05). In contrast, TRP levels in both saliva and serum were significantly reduced (P < .001). Correlation analyses revealed that TRP levels were negatively associated with periodontal disease severity, whereas the salivary KYN/TRP ratio, 3OHKYN, HIF-1 alpha, 8-OHdG, and TNF-alpha were positively associated (P < .05). Strong correlations were observed between the saliva and serum compartments, with a strong positive relationship between salivary and serum TRP and a moderate correlation for the KYN/TRP ratios. Multivariate logistic regression identified salivary KYN/TRP ratio and HIF-1 alpha as independent predictors of periodontitis after adjusting for age and gender, with male gender also emerging as a significant factor (P < .05). Overall, the findings suggest that KP alterations, hypoxia, and oxidative stress are closely interconnected in periodontal inflammation. However, due to the cross-sectional design, these associations should not be interpreted as causal. The KP and hypoxia pathways may serve as potential non-invasive biomarkers for periodontitis.