Bidirectional relationship between apical periodontitis and liver fibrosis: study of inflammasomes, cytokines and CD20 antibody

• Grant number: 20/09695-5
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2021
• End date: June 30, 2023
• Field of knowledge: Health Sciences - Dentistry - Endodontics
• Principal Investigator: Luciano Tavares Angelo Cintra
• Grantee: Luciano Tavares Angelo Cintra
• Host Institution: Faculdade de Odontologia (FOA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil
• Associated researchers: Edilson Ervolino

Abstract

The interrelationship between systemic disease and the development and progression of oral infections such as apical periodontitis has been the subject of intense study in recent years, especially by our research group. The aim of this study is to evaluate the interrelationship between apical periodontitis (AP) associated with liver fibrosis (LF) through the study of NLRP3 inflammasome, IL-1², IL-18, IL-17 and CD20 antibody in Wild-Type and Nlrp3tm1Hhf /J knockout mice. Forty Wild-Type (WT) mice will be divided into 4 groups (n=10): Group WT (control); AP-WT Group: mice with AP; LF-WT Group: mice with LF; AP+LF-WT group: mice with LF and AP. Another forty Nlrp3tm1Hhf/J knockout mice (KO) will be divided into 4 groups (n=10): Group KO (control); AP-KO Group: mice with AP; LF-KO Group: mice with LF; AP+LF-KO Group: mice with LF and AP. LF will be chemically and surgically induced. Carbon tetrachloride (CCl4) will be administered at a dosage of 0.5µL /g body weight twice a week, intraperitoneally, and throughout the experiment (60 days). Thirty days after the beginning of drug administration, a surgical procedure for bile duct ligation will be performed. Next, AP will be induced by pulpal exposure of the first and second right upper and lower molars. After another 30 days the animals will be euthanized and the jaws, as well as the livers will be collected for light microscopy analysis. Liver tissue will be analyzed by Hematoxylin-Eosin (H&E) and Picrosirius Red staining for check the degree of liver fibrosis. The mandibles will be processed for histological analysis in H&E. Both organs will be subjected to immunohistochemical analysis for NLRP3, IL-1², IL-18, IL-17 and CD20. The results will be analyzed and compared by specific statistical tests for each case with a significance level of 5% (p <0.05). (AU)