INFLUENCE OF ANXIOLYTIC AND ANTIDEPRESSANT DRUGS ON BONE MICROARCHITECTURE AND ITS INTERACTION WITH ORTHODONTIC TOOTH MOVEMENT: HISTOLOGICAL, MICROTOMORAPHY AND GENIC ANALYSIS

• Grant number: 24/08099-0
• Support Opportunities: Regular Research Grants
• Duration: November 01, 2024 - October 31, 2026
• Field of knowledge: Health Sciences - Dentistry - Orthodontics
• Principal Investigator: Maria Bernadete Sasso Stuani
• Grantee: Maria Bernadete Sasso Stuani
• Host Institution: Faculdade de Odontologia de Ribeirão Preto (FORP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated researchers: Mírian Aiko Nakane Matsumoto ; Valéria Oliveira Pagnano de Souza
• Associated scholarship(s): 24/18574-8 - INFLUENCE OF ANXIOLYTIC AND ANTIDEPRESSANT DRUGS ON BONE MICROARCHITECTURE AND ITS INTERACTION WITH ORTHODONTIC TOOTH MOVEMENT: HISTOLOGICAL, MICROTOMOGRAPHY AND GENIC ANALYSIS, BP.TT

Abstract

Orthodontic tooth movement (MDO) occurs when controlled force is applied for a certain period, generating inflammation, which results in bone remodeling. Some studies demonstrate that systemic medications can interfere with the course of inflammation and, indirectly, affect MDO and bone metabolism. Certain antidepressants have secondary anti-inflammatory action, however, there are no studies relating benzodiazepines such as Clonazepam and selective serotonin reuptake inhibitors (SSRIs) such as Escitalopram and their interaction with oral bone microarchitecture. The objective of this study is to evaluate the effect of these drugs on bone microarchitecture, tooth movement rate and orthodontically induced root resorption. Two hundred and forty Wistar rats, (males = 120 animals and females = 120 animals), will be divided into 5 groups: GMV - group subjected to tooth movement; GPL - placebo group with daily doses of saline solution (0.9% NaCL) by gavage; GCl - Daily doses of Clonazepam (Roche do Brasil S.A., São Paulo, Brazil) and GOx - Daily doses of Escitalopram Oxalate at a concentration of 10mg/kg diluted in 2ml of saline solution; via IP. In each group, the right hemi-maxilla will be subjected to orthodontic tooth movement and the left hemi-maxilla will serve as control. The MDO will be performed with NiTi springs with dental anchorage for 3, 7, 14 and 21 days and verified through metric evaluation in microtomography. Bone mineral density and root resorption will be evaluated using microcomputed tomography, histopathological and immunohistochemical exams and analysis of cytokines in blood plasma using the Multiplex Luminex technique. Histological and immunohistochemical analysis will be performed for TRAP, RANK, RANKL and OPG, as well as PCR-RT for the genes Tnfrsf11a (Rank), Tnfsf11 (Rankl), Tnfrsf11b (Opg), and the endogenous control genes GAPDH (glyceraldehyde- 3-phosphate dehydrogenase) and b-actin (Beta-actin). Using the luminex technique, the presence of inflammatory cytokines will be assessed. Therefore, this research may contribute to the production of scientific evidence on the interaction between anxiolytic and antidepressant drugs, bone metabolism and the occurrence of side effects throughout orthodontic treatment, presenting both interest academic and clinical, with regard to guiding the conduct of Orthodontists during the treatment of patients using psychoactive drugs. (AU)