Compartment-specific oxidative stress signatures in oral leukoplakia: a systematic review of local and systemic biomarkers.

Authors

Cristina Estornut, Ulrikke Pauline Clark-Utvik, Nicla Flacco, Pilar Ribera, Germán Sánchez-Herrera, Martín Pérez-Leal

Published in

Frontiers in physiology. Volume 17. Pages 1851447. Epub Jun 03, 2026.

Abstract

Oral leukoplakia (OLK) is one of the most common potentially malignant disorders of the oral mucosa. Oxidative stress is increasingly recognized as a key factor in its pathogenesis and malignant transformation, but the consistency of biomarker alterations across biological compartments remains unclear.
To evaluate compartment-specific oxidative stress alterations across local (tissue, saliva) and systemic (blood, plasma, serum) environments in OLK by synthesizing evidence on biomarker levels in these biological compartments.
A systematic search was conducted in PubMed, Web of Science and Scopus, following PRISMA guidelines. Studies were included if they compared oxidative stress biomarkers between OLK patients and healthy controls. Data were qualitatively synthesized, and study quality was assessed using the Newcastle-Ottawa Scale, ROBINS-I (Cochrane), and AXIS. The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) under registration number CRD42023438437.
Fifteen studies were included (n = 804). Oxidative damage markers such as malondialdehyde (MDA) and 8-OHdG were consistently elevated in OLK patients across tissue, serum, plasma, blood, and saliva. Enzymatic antioxidants such as GPx, SOD, and CAT were generally reduced, whereas tissue levels of glutathione (GSH) were elevated, suggesting a local compensatory response. Total antioxidant capacity (TAS/TAC) was decreased systemically. Notably, antioxidant responses differed across biological compartments, with increased tissue GSH contrasting with systemic depletion.
The available evidence supports a consistent redox imbalance in OLK characterized by increased oxidative damage and impaired systemic antioxidant defenses. Salivary and serum biomarkers, particularly MDA and 8-OHdG, show promise as non-invasive indicators of oxidative stress and disease progression. However, methodological heterogeneity and small sample sizes limit clinical translation. Standardized protocols and longitudinal studies are needed to validate these biomarkers.

PMID:
42311327
Bibliographic data and abstract were imported from PubMed on 14 Sep 2026.

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