EVALUATION OF THE IMMUNOPHARMACOLOGIC EFFECT OF EPOXI HYDROLASE INHIBITOR (TPPU) TO CONTROL BONE LOSS

• Grant number: 15/23556-0
• Support type: Regular Research Grants
• Duration: March 01, 2016 - February 28, 2018
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Marcelo Henrique Napimoga
• Grantee: Marcelo Henrique Napimoga
• Home 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

Epoxyeicosatrienoic acids (EETs) are products of arachidonic acid metabolism catalyzed by cytochrome P450 epoxygenases. These small molecules are autocrine and paracrine lipid mediators with important roles in inflammation, cardiovascular function, and angiogenesis. Recent evidence has highlighted that EETs could represent a novel therapeutic strategy for osteoclast-related disorders. The presence of EETs in tissues and their metabolism by soluble epoxide hydrolase (sEH) to 1,2-diols were first reported 30 years ago. However, appreciation of their importance in cell biology and physiology has greatly accelerated over the past decade with the discovery of metabolically stable inhibitors of sEH, such as TPPU (1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl)), the commercial availability of EETs, and the development of analytical methods for the quantification of EETs and their diols. The present study aimed to investigate whether sEH inhibitor (TPPU) may modulate the bone resorption in a periodontitis mouse model as well as, to elucidate the involved molecular mechanisms. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

NAPIMOGA, M. H.; ROCHA, E. P.; TRINDADE-DA-SILVA, C. A.; DEMASI, A. P. D.; MARTINEZ, E. F.; MACEDO, C. G.; ABDALLA, H. B.; BETTAIEB, A.; HAJ, F. G.; CLEMENTE-NAPIMOGA, J. T.; INCEOGLU, B.; HAMMOCK, B. D. Soluble epoxide hydrolase inhibitor promotes immunomodulation to inhibit bone resorption. JOURNAL OF PERIODONTAL RESEARCH, v. 53, n. 5, p. 743-749, OCT 2018. Web of Science Citations: 1.

TRINDADE-DA-SILVA, CARLOS ANTONIO; BETTAIEB, AHMED; NAPIMOGA, MARCELO HENRIQUE; LEE, KIN SING STEPHEN; INCEOGLU, BORA; UEIRA-VIEIRA, CARLOS; BRUUN, DONALD; GOSWAMI, SUMANTA KUMAR; HAJ, FAWAZ G.; HAMMOCK, BRUCE D. Soluble Epoxide Hydrolase Pharmacological Inhibition Decreases Alveolar Bone Loss by Modulating Host Inflammatory Response, RANK-Related Signaling, Endoplasmic Reticulum Stress, and Apoptosis. Journal of Pharmacology and Experimental Therapeutics, v. 361, n. 3, p. 408-416, JUN 1 2017. Web of Science Citations: 6.