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

**Authors:** Monique Gonçalves da Costa, Eduardo Dallazen, Mateus Diego Pavelski, Izabela Fornazari Delamura, Larissa Victorino Sampaio, Antonio Hernandes Chaves-Neto, Leonardo Perez Faverani

PMC · DOI: 10.1007/s00784-026-06834-7 · 2026-03-23

## TL;DR

This study compares two ozone therapy methods after tooth extraction, finding that ozonized oil reduces pain and shows biochemical benefits compared to a placebo.

## Contribution

The study introduces ozonized oil as a non-pharmacological adjuvant for postoperative recovery after molar extraction.

## Key findings

- Ozonized oil significantly reduced postoperative pain compared to placebo.
- Ozonized oil showed reduced oxidative damage and increased antioxidant markers in saliva.
- Subperiosteal ozone gas showed no significant clinical or biochemical benefits.

## Abstract

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.

## Full-text entities

- **Genes:** NXF1 (nuclear RNA export factor 1) [NCBI Gene 10482] {aka MEX67, TAP}, ALB (albumin) [NCBI Gene 280717], GPT (glutamic--pyruvic transaminase) [NCBI Gene 2875] {aka AAT1, ALT, ALT1, GPT1, SGPT}, CPAT1 (cerebral palsy, ataxic 1) [NCBI Gene 60502] {aka ACP}, UOX (urate oxidase (pseudogene)) [NCBI Gene 391051] {aka UOXP, URICASE}, SLC17A5 (solute carrier family 17 member 5) [NCBI Gene 26503] {aka AST, ISSD, NSD, SD, SIALIN, SIASD}, PC (pyruvate carboxylase) [NCBI Gene 5091] {aka PCB}, ALPP (alkaline phosphatase, placental) [NCBI Gene 250] {aka ALP, PALP, PLAP, PLAP-1}
- **Diseases:** odontogenic tumors (MESH:D009808), tissue injury (MESH:D017695), Trismus (MESH:D014313), hepatic injury (MESH:D056486), anxiety (MESH:D001007), surgical (MESH:D007431), Edema (MESH:D004487), hypersensitivity (MESH:D004342), inflammation (MESH:D007249), cysts (MESH:D003560), cutaneous fungal infections (MESH:D009181), periodontal disease (MESH:D010510), PC (MESH:D011488), reduction in mouth opening (MESH:D009059), trauma (MESH:D014947), infection (MESH:D007239), Pain (MESH:D010146), cytotoxic (MESH:D064420), OZO-OIL (MESH:D001528), postoperative pain (MESH:D010149), substance abuse (MESH:D019966)
- **Chemicals:** OIL (MESH:D009821), penicillin (MESH:D010406), hydrogen peroxide (MESH:D006861), p-NP (MESH:C024836), UA (MESH:D014527), water (MESH:D014867), NaCl (MESH:D012965), O3 (MESH:D010126), TBARS (MESH:D017392), amoxicillin (MESH:D000658), clindamycin (MESH:D002981), aldehydes (MESH:D000447), GAS (MESH:D005708), OZO-OIL (-), allantoin (MESH:D000481), chlorhexidine digluconate (MESH:C010882), Lipid (MESH:D008055), epinephrine (MESH:D004837), AU (MESH:D006046), chlorhexidine (MESH:D002710), p-NPP (MESH:C008644), alcohol (MESH:D000438), nylon (MESH:D009757), Fe (MESH:D007501), magnesium chloride (MESH:D015636), 2,4-dinitrophenylhydrazine (MESH:C004787), mepivacaine (MESH:D008619)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13009080/full.md

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Source: https://tomesphere.com/paper/PMC13009080