Analysis of different concentrations of ozonized sunflower oil and its effects on local adjuvant therapy of zoledronate-induced mandibular osteonecrosis: a study in senile female rats

Abstract

Medication-related osteonecrosis of the jaw (MRONJ) is an adverse effect caused by anti-resorptive and anti-angiogenic drugs. Its etiopathology, as well as its prevention, control, and cure, remain a challenge today. Concomitantly, ozone therapy has gained prominence due to its antimicrobial, anti-inflammatory, analgesic, and even disinfectant properties. Joining these points, this project will aim to seek the best concentration of ozonized oil for tissue repair, which is innocuous for the host and manages to control or even cure MRONJ. For that, 35 female Wistar rats, 18 months of age, will be divided into five experimental groups: SAL, ZOL, ZOL+OZN500, ZOL+OZN600, and ZOL+OZN700 groups. The groups treated with zoledronate (ZOL, ZOL+OZN500, ZOL+OZN600, and ZOL+OZN700) will receive the application at a dose of 100¼g/kg, while in the SAL group, the rats will be subjected to applications of 0.9% sodium chloride solution to mimic the stress suffered by other animals, both administrations should be carried out every three days for seven weeks. After three weeks from the start of drug therapy, the animals will undergo extraction of the lower left first molar; at this time, local therapy with ozonized sunflower oil will be started in the designated groups, following the protocol of 30ml - 500 mEq/kg (ZOL+OZN500 group), 30ml - 600 mEq/kg (ZOL+OZN600 group), and 30ml - 700 mEq/kg (ZOL+OZN700 group), at a concentration of 0.3 mg/kg, for 2 minutes in periods of 0, 2 and 4 days after surgery. Euthanasia will be carried out 28 days after extraction, and the mandibles will then be removed, reduced, and prepared for micro-CT and decalcified tissue analysis. In addition, clinical analyzes will be carried out with photographic documentation of the alveolus at the end of the experimental time and anatomopathological analysis of the main metabolizing organs. Data will be submitted to the normality curve to determine the most appropriate test (p<0.05).(AU)