Autor(es)

Trindade-da-Silva, Carlos Antonio ; Yang, Jun ; Fonseca, Flavia ; Pham, Hoang ; Napimoga, Marcelo Henrique ; Abdalla, Henrique Ballassini ; Aver, Geanpaolo ; De Oliveira, Marcio Jose Alves ; Hammock, Bruce D. ; Clemente-Napimoga, Juliana Trindade

• Tipo de documento: Artigo Científico
• Fonte: BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS; v. 1869, n. 2, p. 10-pg., 2023-11-20.

Resumo

Rheumatoid arthritis is a common systemic inflammatory autoimmune disease characterized by damage to joints, inflammation and pain. It is driven by an increase of inflammatory cytokines and lipids mediators such as prostaglandins. Epoxides of polyunsaturated fatty acids (PUFAs) are lipid chemical mediators in a group of regulatory compounds termed eicosanoids. These epoxy fatty acids (EpFA) have resolutive functions but are rapidly metabolized by the soluble epoxide hydrolase enzyme (sEH) into the corresponding diols. The phar-macological inhibition of sEH stabilizes EpFA from hydrolysis, improving their half-lives and biological effects. These anti-inflammatory EpFA, are analgesic in neuropathic and inflammatory pain conditions. Nonetheless, inhibition of sEH on arthritis and the resulting effects on eicosanoids profiles are little explored despite the physiological importance. In this study, we investigated the effect of sEH inhibition on collagen-induced arthritis (CIA) and its impact on the plasma eicosanoid profile. We measured the eicosanoid metabolites by LC-MS/MS-based lipidomic analysis. The treatment with a sEH inhibitor significantly modulated 11 out of 69 eicosanoids, including increased epoxides 12(13)-EpODE, 12(13)-EpOME, 13-oxo-ODE, 15-HEPE, 20-COOH-LTB4 and de-creases several diols 15,6-DiHODE, 12,13-DiHOME, 14,15-DiHETrE, 5,6-DiHETrE and 16,17-DoPE. Overall the inhibition of sEH in the rheumatoid arthritis model enhanced epoxides generally considered anti-inflammatory or resolutive mediators and decreased several diols with inflammatory features. These findings support the hypothesis that inhibiting the sEH increases systemic EpFA levels, advancing the understanding of the impact of these lipid mediators as therapeutical targets. (AU)

• Processo FAPESP: 19/01151-9 - Avaliação do efeito imunomodulador e neuroprotetor do inibidor de epóxi hidrolase, TPPU, na hipernocicepção inflamatória persistente induzida pela artrite na articulação temporomandibular de ratos.
• Beneficiário: Carlos Antonio Trindade da Silva
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 19/21176-6 - Avaliação do mecanismo intracelular no efeito imunomodulador dos ácidos epoxieicosatrienóicos e da inibição da epoxide hydrolase solúvel em um modelo de artrite
• Beneficiário: Carlos Antonio Trindade da Silva
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado
• Processo FAPESP: 17/22334-9 - Uso de sistemas de liberação de fármacos para o desenvolvimento e aplicabilidade de agentes anti-inflamatórios com potencial efeito imunomodulador e neuroprotetor
• Beneficiário: Marcelo Henrique Napimoga
• Modalidade de apoio: Auxílio à Pesquisa - Temático