Abstract Aim: To evaluate changes in salivary antioxidant markers (Kelch-like ECH-associated protein 1 KEAP1, nuclear factor erythroid 2-related factor 2 NRF-2) and pro-inflammatory cytokines (nuclear factor-kappa B NF-κB, interleukin IL-1β, and tumor necrosis factor alpha TNF-α) in head and neck cancer (HNC) patients developing oral mucositis (OM) during chemo-radiotherapy (CRT). Methods: Fifty HNC patients scheduled for CRT and 50 age-matched healthy controls were recruited. Unstimulated saliva was collected at baseline (Day 0) and after 30 days of CRT (Day 30). OM severity was graded based on World Health Organization criteria. Biomarker levels were quantified using enzyme-linked immunosorbent assay. Data normality was analyzed by using the Shapiro–Wilk test. Group comparisons were analyzed using one-way analysis of variance with Tukey’s post hoc test. Results: OM severity significantly increased from Day 0 to Day 30 ( P < 0.01). Pro-inflammatory markers were elevated in OM patients at Day 30 compared to Day 0 and healthy controls: NF-κB (2.6 ± 0.14; 2.5 ± 0.14; 1.5 ± 0.07 ng/mL), IL-1β (129 ± 2.82; 125 ± 2.82; 75 ± 7.07 pg/mL), and TNF-α (280 ± 7.07; 250 ± 2.82; 177 ± 6.3 pg/mL; P < 0.0001). Antioxidant marker levels were reduced: KEAP1 (2.3 ± 0.07; 2.9 ± 0.2; 5.0 ± 0.63 ng/mL) and NRF-2 (374 ± 7.07; 466 ± 13.4; 800 ± 6.3 pg/mL; P < 0.0001). Conclusion: This first longitudinal assessment of salivary KEAP1/NRF-2 in HNC patients showed reduced antioxidant defense and elevated pro-inflammatory cytokine levels (NF-κB, TNF-α, and IL-1β) at Day 30, indicating OM progression. Early therapeutic targeting of these biomarkers with novel antioxidant and anti-inflammatory agents may help reduce the severity of OM, minimizing treatment-related toxicity and ultimately improving the overall survival of these patients.
Dharman et al. (Thu,) studied this question.