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Analysis of insulin resistance, morphology and inflammatory signaling pathway in the placenta of rats with apical periodontitis

Grant number: 23/00536-0
Support Opportunities:Scholarships in Brazil - Master
Effective date (Start): May 01, 2023
Effective date (End): April 30, 2025
Field of knowledge:Health Sciences - Dentistry - Social and Preventive Dentistry
Principal Investigator:Doris Hissako Matsushita
Grantee:Ana Carla T Ywabuchi Nobumoto
Host Institution: Faculdade de Odontologia (FOA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil


In recent years, the relationship between oral inflammation and systemic disorders has become an area of great interest in the medical and dental scientific community. In this context, studies have shown that maternal periodontal disease (PD) is associated with adverse gestational outcomes, such as low birth weight and preterm delivery. Furthermore, it was verified that periodontal pathogens induce alterations in the placental structure. However, the literature is scarce in terms of studies that investigated the relationship between maternal apical periodontitis (AP) and adverse pregnancy outcomes. AP is an oral inflammatory process in the region of the apex of the dental root associated with an increase in inflammatory cytokines that may contribute to systemic changes. The aim of the present study will be to investigate insulin resistance and the morphological aspects and inflammatory signaling pathway in the placenta of rats with AP and to investigate the effects of maternal AP on the health of the neonate. Therefore, the 24 Wistar rats (2 months old) will be divided into 3 groups: 1) control rats; 2) rats with 1 AP induced in the right upper 1st molar; 3) rats with 4 APs induced in the 1st and 2nd upper and lower molars on the right side. AP will be induced using a carbon steel drill with a 0.1 mm ball at the end. After 30 days of pulp exposure, female rats from all groups will be placed for mating. The rats will be euthanized on the twentieth day of pregnancy to carry out the following experiments: 1) placental weight; 2) histology of the placenta; 3) glycemia by the glucose-oxidation method; 4) insulinemia by the ELISA method; 5) insulin resistance by HOMA-IR calculation; 6) JNK, IKK alpha/beta, NF-kB p50 (Ser337) and NF-kB p65 (Ser276) phosphorylation status in the placenta using the Western blotting technique; 7) protein content of JNK, IKK alpha/beta, NF-kB p50 (Ser337), NF-kB p65 (Ser276) and TNF-alpha in the placenta using the Western blotting technique. Regarding the newborns, the following analyzes will be carried out: 1) analysis of the number, weight and cephalo-anal size of the newborns; 2) capillary blood glucose; 3) evaluation of the protein content of TNF-± in the liver of neonates using the Western blotting technique. For the statistical analysis, the normality of the data will be statistically verified. Will be performed by analysis of variance (ANOVA), followed by the Tukey test. Results will be considered statistically significant when p < 0.05, using the statistical software Graph Pad Prism version 7.0 (GraphPad Software Inc., San Diego, CA, USA). Values will be expressed as mean ± standard error of mean (SEM).

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