Salivary Oxidative-Antioxidant Profile Following Adjunctive Gaseous Ozone Administration in Non-Surgical Periodontal Treatment: A Randomized Controlled Trial

<b>Background</b>: Periodontitis is associated with increased oxidative stress, which may impair treatment outcomes. Ozone therapy has shown promise in reducing oxidative stress and improving periodontal health. This study examined the impact of adjunctive gaseous ozone administration on salivary oxidative stress markers in patients with periodontitis stages II-IV and grades A-C undergoing non-surgical periodontal treatment (NSPT). <b>Methods</b>: Ninety patients with periodontitis were randomly allocated to either the test group (NSPT with gaseous ozone administration) or the control group (NSPT alone) using computer-generated randomization. The OzoneDTA system was used to deliver ozone at 2100 ppm for 60 s per site once weekly for 4 weeks. Clinical periodontal parameters (probing depth [PD], clinical attachment level [CAL], plaque index [PI], gingival index [GI]) and salivary oxidative stress markers (malondialdehyde [MDA], total antioxidant capacity [TAC], superoxide dismutase [SOD]) were assessed by blinded examiners at baseline, 3, and 6 months post-treatment. <b>Results</b>: Mixed ANOVA revealed significant three-way interactions between time, treatment, and stage or grade for clinical and biochemical measures (<i>p</i> < 0.001). The test group exhibited significant improvements in TAC (mean difference: 0.45 ± 0.12 mmol/L, <i>p</i> = 0.002), MDA (-0.38 ± 0.09 nmol/mL, <i>p</i> = 0.001), and SOD (65 ± 18 U/mL, <i>p</i> < 0.001) compared with the control group, with more pronounced effects in stages III and IV. Large effect sizes (Cohen's d > 0.8) were observed for the test group between baseline and 6 months for all markers. <b>Conclusions</b>: Gaseous ozone administration as an adjunct to NSPT can effectively improve clinical periodontal parameters and salivary oxidative stress markers, particularly in stages III and IV periodontitis. The enhanced outcomes may be attributed to ozone's antimicrobial and immunomodulatory properties, which synergistically reduce oxidative stress and promote periodontal healing.