Effect of intraoral and extraoral photobiomodulation on salivary oxidative stress and inflammatory cytokines in patients with radiotherapy-induced oral mucositis

Photobiomodulation (PBM) is an evidence-based approach for managing oral mucositis (OM) in patients undergoing head and neck radiotherapy (RT), though its biological mechanisms remain under investigation. This study evaluated salivary oxidative stress (OS) and inflammatory biomarkers in patients with head and neck squamous cell carcinoma (HNSCC) who received intraoral (IOPBM, n = 10) or extraoral PBM (EOPBM, n = 8) as supportive therapy during radiotherapy, and not as a cancer treatment. Preventive IOPBM/EOPBM were applied five times weekly from RT initiation until OM healing. Twenty healthy individuals served as the control group. Unstimulated saliva was collected at pre-, mid-, and final-RT (last RT session) to assess myeloperoxidase (MPO), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), interleukin-6 (IL-6), and interleukin-10 (IL-10). HNSCC patients exhibited altered oxidative and inflammatory biomarker profiles during RT. MDA levels showed a transient increase at mid-RT (p 0.05). MPO activity was significantly higher at all RT time points and across OM severity grades compared with CT (p < 0.05–0.01). In contrast, SOD activity were consistently elevated throughout RT in PBM-treated patients compared with CT (p < 0.001), and GSH levels increased at mid-RT (p < 0.01). IL-6 and IL-10 levels decreased from pre- to final-RT compared to CT (p < 0.05). Clinically, all patients developed OM, although fewer than 40% experienced severe OM. These findings suggest that PBM enhances antioxidant defenses and modulates inflammatory responses, supporting its role in reducing RT-induced oral toxicity.