Effect of Chronic Excessive Physical Exercise (Overtraining) on Apical Periodontitis: A Mouse Study

• Grant number: 24/16085-0
• Support Opportunities: Scholarships in Brazil - Master
• Start date: April 01, 2025
• End date: February 28, 2026
• Field of knowledge: Health Sciences - Dentistry - Endodontics
• Principal Investigator: Gisele Faria
• Grantee: Andréia Bosco Boaventura
• Host Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil

Abstract

Regular physical exercise is widely recognized for its health benefits, including the prevention and treatment of various chronic conditions. However, when performed excessively and without adequate recovery, it can lead to overtraining, a condition that increases systemic levels of pro-inflammatory mediators such as IL-1¿, IL-6, and TNF-¿, potentially compromising the individual's immune response. The development and progression of apical periodontitis (AP), characterized by inflammation and destruction of periapical tissues due to infection in the root canal system, are influenced by the host's immune response and certain systemic conditions. In addition to changes in the periapical region, the presence of AP elevates systemic levels of pro-inflammatory mediators. Considering those evidence, we hypothesize (1) that overtraining may promote the development of larger periapical lesions and (2) that individuals with AP undergoing overtraining will have higher levels of systemic pro-inflammatory mediators compared to those with only one of these conditions. To test this hypothesis, 60 male wild-type (WT) C57BL/6 mice, aged 7 weeks, will be used. The mice will first undergo an adaptation phase to treadmill exercise tailored for rodents. They will then be distributed into six groups (n=10): SE (sedentary without AP), SE+AP (sedentary with AP), TRA (regular aerobic training without AP), TRA+AP (regular aerobic training with AP), OT (overtraining without AP), and OT+AP (overtraining with AP). The TRA and OT protocols will last eight weeks. After four weeks of training, AP will be induced by opening the crowns of the bilateral lower first molars, followed by four more weeks of training before euthanasia. Blood and hemimandibles will be collected. Analyses will include determining serum concentrations of IL-1¿, IL-6, TNF-¿, and IL-10 by ELISA, quantification of periapical bone resorption by micro-computed tomography, evaluation of inflammation in the AP region in histological sections stained with hematoxylin and eosin, immunostaining of IL-1¿, IL-6, TNF-¿, and IL-10, analysis of gene expression related to inflammation and osteoclastogenesis in the periapical region by RT-qPCR (IL-1¿, IL-6, TNF-¿, RANKL, OPG, cathepsin K), and determining the presence of osteoclasts in the AP region through tartrate-resistant acid phosphatase (TRAP) assays. Statistical tests will be selected according to the distribution and homoscedasticity of the data, with a significance level of 5%.