Evaluation of the Impact of the Soluble Epoxide Hydrolase Inhibitor, TPPU, on Production of Specialized Pro-resolving Lipid Mediators as a Pharmacological Approach for the Treatment of Inflammatory Disorders

• Grant number: 19/22645-0
• Support type: Scholarships abroad - Research Internship - Post-doctor
• Effective date (Start): March 01, 2020
• Effective date (End): February 28, 2021
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Marcelo Henrique Napimoga
• Grantee: Henrique Ballassini Abdalla
• Supervisor abroad: Thomas E. Van Dyke
• 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
• Local de pesquisa : Forsyth Institute, United States
• Associated to the scholarship: 19/04276-7 - The use of micro-needles coated with drugs for the control of pain and inflammation, BP.PD

Abstract

Specialized Pro-resolving lipid Mediators (SPMs) are metabolites of polyunsaturated fatty acids (PUFA), including arachidonic acid (AA) and the omega-3 PUFA eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). This class of lipid mediators possesses physiological activity that limits the onset of inflammation and actively resolves chronic inflammation through binding to specific receptors on inflammatory and other cells. Lipoxins, Resolvins of the E and D series and Maresins are endogenous mediators classified as SPMs and are synthesized in the resolution phase of the inflammatory process. Soluble epoxide hydrolase (sEH) is an enzyme that converts epoxyeicosatrienoic acids (EETs) produced by cytochrome P450 in a less active form. It has been shown that EETs demonstrate potent antinociceptive and anti-inflammatory actions. However, because of their rapid metabolization, this pathway has yet to be targeted for pharmacological intervention. Our data suggest that inhibitors of sEH represent a strategy to increase the levels of EETs, such as the inhibitor (1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea [TPPU]). The aim of this study is to investigate whether treatment with sEH inhibitor will lead to an increase in production of SPMs. It has been shown that even small increases in SPMs prevents excess inflammation, and reverses chronic inflammation in a variety of inflammatory diseases. Given the significant public health impact of inflammation-associated diseases, new therapeutic approaches are welcome, especially those that are not immunosuppressive, but have immunoresolvents properties.