Clinical effects of two ozone therapy administration methods following mandibular third molar extraction: a parallel-group randomized clinical trial with exploratory salivary biomarker assessment

Some non-drug methods have been used as adjuncts to minimize tissue damage after third molar extractions, including ozone therapy, although there is no consensus on the most efficient protocol. to compare two ozone therapy administration protocols regarding clinical parameters (edema, pain, maximum mouth opening) and salivary biomarkers of tissue injury and redox state. This randomized, parallel-group clinical trial with blinded outcome assessment included thirty-five volunteers (45 mandibular third molars; 15 teeth per group). Participants were allocated to OZO-GAS (0.1 mL of subperiosteal ozonized gas), OZO-OIL (600 mEq of topical ozonized oil), or PLACEBO, administered immediately postoperatively and after 2 days. Outcome evaluation was performed by an examiner blinded to group allocation. Clinical outcomes were recorded at 24 h, 48 h, and 7 days, and unstimulated saliva was collected at the same time for spectrophotometric analyses. The OZO-OIL group showed greater efficacy in reducing postoperative pain compared with PLACEBO (p < 0.05; Holm–Sidak). At 48 h postoperatively, OZO-OIL was associated with reduced salivary protein carbonyls and TBARS, alongside increased uric acid levels, compared with the PLACEBO group (p < 0.05). No consistent clinical or biochemical benefits were observed for the OZO-GAS protocol, and salivary related enzymes (AST, ALT, and ALP) suggested a less favorable biochemical profile in this group . Topical ozonized oil improved postoperative pain following mandibular third molar extraction and was associated with trends toward reduced oxidative damage and enhanced antioxidant defense compared with placebo, while gas administration showed no comparable benefits. The observed biochemical effects should be considered exploratory and correlated with the clinical findings. Ozonized oil represents a simple, non-pharmacological adjuvant capable of enhancing postoperative recovery after third molar extraction.