Assessment of the impact of the absence of the soluble epoxy hydrolase enzyme in the gingival tissue of mice in senescence.

• Grant number: 23/12079-2
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2024
• End date: August 31, 2026
• Field of knowledge: Health Sciences - Dentistry - Periodontology
• Principal Investigator: Henrique Ballassini Abdalla
• Grantee: Gisele Barreto de Freitas
• Host Institution: Centro de Pesquisas Odontológicas São Leopoldo Mandic. Faculdade São Leopoldo Mandic (SLMANDIC). Sociedade Regional de Ensino e Saúde S/S Ltda (SRES). Campinas , SP, Brazil

Abstract

The prevalence and severity of periodontitis increase with aging. The reasons for the age-related increase in bone loss in periodontal disease are still not fully understood. It is hypothesized that changes in susceptibility to periodontitis with age can be explained by exposure to pro-inflammatory conditions and the inability of cell healing and tissue regeneration. Eicosanoids, a group of lipid mediators (LMs), are oxidized derivatives of arachidonic acid (ARA) metabolism via oxidative pathways, the enzymes cyclooxygenase (COX), lipoxygenase (LOX) or cytochrome P450 (CYP450). The resulting bioactive molecules, with distinct biological functions, are largely produced in inflammation. Although much is known about the metabolism of polyunsaturated fatty acids (PUFAs) derived from omega-3 through the COX and LOX enzymatic pathways, the CYP450 pathway must be explored. Remarkably, the epoxides of long-chain polyunsaturated fatty acids (EpFA) generated by the CYP450 pathway are essential bioactive lipids with immunomodulatory actions in inflammation. Most of these LMs are short-lived due to their rapid metabolization to inactive diols in the presence of the enzyme soluble epoxy hydrolase (sEH), losing their ability to resolve inflammation. Within this context, this project aims to investigate the impact of the absence of the sEH enzyme on bone levels and parameters and to evaluate the inflammatory parameters related to the aging of the gingival tissue in an in vivo senescence model. For this, young and old C57BL/6 (wild-type) and sEH-/- [knockout (KO)] mice, equally distributed between males and females, will be induced to the senescence protocol. The protocol considers young animals with three months of life and senescent animals with 20 months of life. Gingival tissue, maxilla, and mandible samples will be collected at the end of each protocol. Alveolar bone loss will be measured using methylene blue and computed microtomography (µCT). Still, the gene expression of osteolytic inflammatory mediators, Rankl, Tnf±, Il1², Il6, Il17a, and Mmp2, as well as markers of cellular senescence, Cdkn1a (p21), Cdkn2a (p16), Tp53 and Glb1 (beta-galactosidase) will be evaluated. Through this study, it is hoped to elucidate the role of the sEH enzyme in senescence and its impact on bone parameters and the inflammatory cascade associated with aging. The data to be obtained also seek to highlight new therapeutic targets that can control alveolar bone loss related to senescence.