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Evaluation of the immunomodulatory and neuroprotective effect of the epoxy hydrolase inhibitor, TPPU, on persistent inflammatory hypernociception induced by arthritis in the temporomandibular joint of rats.

Grant number: 19/01151-9
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): April 01, 2019
Effective date (End): March 31, 2023
Field of knowledge:Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
Principal Investigator:Juliana Trindade Clemente Napimoga
Grantee:Carlos Antonio Trindade da Silva
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
Associated research grant:17/22334-9 - Use of drug delivery systems for the development and application of anti-inflammatory agents with potential immunomodulatory and neuroprotective effects, AP.TEM
Associated scholarship(s):19/21176-6 - Evaluation of intracellular mechanism of the immunomodulatory effect of epoxyeicosatrienoic acids and the inhibition of soluble epoxide hydrolase in a arthritis model, BE.EP.PD


Epoxy-eicosatrienoic acids (EETs) are products of arachidonic acid metabolism catalyzed by epoxygenases of cytochrome P450. EETs have important biological activity, including anti-inflammatory, neuroprotective and neuromodulatory effects. EETs have a very short half-life since they are rapidly hydrolyzed by the enzyme soluble epoxy hydrolase (sEH), reducing their bioavailability. Thus, stable inhibitors of sEH, such as 1-trifluoromethoxyphenyl-3- (1-propionylpiperidin-4-yl) (TPPU) have been investigated as a strategy to increase EETs levels in tissues, making their therapeutic use feasible. Rheumatoid arthritis is a chronic and multifactorial inflammatory autoimmune disease that affects synovial joints such as the temporomandibular joint (TMJ). Chronic pain is the foremost reason for seeking TMJ treatment. The cells of the immune system have been shown to participate in the modulation of neural transmission involving painful conditions, a process called the neuroimmune pain interface. This proposal aims to investigate the role of TPPU in the neuroimmune interface involved in sensitization of the central nervous system and development of persistent pain in model of albumin-induced arthritis in TMJ in rats.

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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)
TRINDADE DA SILVA, CARLOS ANTONIO; CLEMENTE-NAPIMOGA, JULIANA TRINDADE; ABDALLA, HENRIQUE BALLASSINI; BASTING, ROSANNA TARKANY; HENRIQUE NAPIMOGA, SOLELY MARCELO. Peroxisome proliferator-activated receptor-gamma (PPAR gamma) and its immunomodulation function: current understanding and future therapeutic implications. EXPERT REVIEW OF CLINICAL PHARMACOLOGY, v. 15, n. 3, p. 9-pg., . (19/01151-9, 17/22334-9, 19/04276-7)

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