Author(s): Ruiz-Miyazawa, Kenji W. ; Staurengo-Ferrari, Larissa ; Pinho-Ribeiro, Felipe A. ; Fattori, Victor ; Zaninelli, Tiago H. ; Badaro-Garcia, Stephanie ; Borghi, Sergio M. ; Andrade, Ketlem C. ; Clemente-Napimoga, Juliana T. ; Alves-Filho, Jose C. ; Cunha, Thiago M. ; Fraceto, Leonardo F. [UNESP] ; Cunha, Fernando Q. ; Napimoga, Marcelo H. ; Casagrande, Rubia ; Verri, Waldiceu A.
Date: 2018
Persistent ID: http://hdl.handle.net/11449/164652
Origin: Oasisbr
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Pesquisa para o Sistema Unico de Saude (PPSUS) grant from Departamento de Ciencia e Tecnologia da Secretaria de Ciencia, Tecnologia e Insumos Estrategicos, Ministerio da Saude (Decit/SCTIE/MS, Brazil)
Fundacao Araucaria and Secretaria Estadual de Saude, Parana (SESA-PR, Brazil)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Financiadora de Estudos e Projetos and Secretaria de Estado da Ciencia, Tecnologia e Ensino Superior do Parana (FINEP/SETI-PR, Brazil)
Central Multiusuario de Laboratorios de Pesquisa da Universidade Estadual de Londrina (CMLP-UEL)
Gout arthritis (GA) is a painful inflammatory disease in response to monosodium urate (MSU) crystals in the joints. 15deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) is a natural activator of PPAR-gamma with analgesic, anti-inflammatory, and pro-resolution properties. Thus, we aimed to evaluate the effect and mechanisms of action of 15d-PGJ(2) nanocapsules (NC) in the model of GA in mice, since a reduction of 33-fold in the dose of 15d-PGJ2 has been reported. Mice were treated with 15d-PGJ(2)-loaded NC, inert NC, free 15d-PGJ(2) (without NC), or 15d-PGJ(2)-loaded NC+GW9662, a PPAR-gamma inhibitor. We show that 15d-PGJ(2)-loaded NC provided analgesic effect in a dose that the free 15d-PGJ(2) failed to inhibiting pain and inflammation. Hence, 15d-PGJ(2)-loaded NC reduced MSU-induced IL-1 beta, TNF-alpha, IL-6, IL-17, and IL-33 release and oxidative stress. Also, 15d-PGJ(2)-loaded NC decreased the maturation of IL-1 beta in LPS-primed BMDM triggered by MSU. Further, 15d-PGJ(2)-loaded NC decreased the expression of the components of the inflammasome Nlrp3, Asc, and Pro-caspase-1, as consequence of inhibiting NF-kappa B activation. All effects were PPAR-gamma-sensitive. Therefore, we demonstrated that 15d-PGJ(2)-loaded NC present analgesic and anti-inflammatory properties in a PPAR-gamma-dependent manner inhibiting IL-1 beta release and NF-kappa B activation in GA. Concluding, 15d-PGJ(2)-loaded NC ameliorates MSU-induced GA in a PPAR-gamma-sensitive manner.
Univ Estadual Londrina, Dept Ciencias Patol, Rod Celso Garcia Cid,Km 380,PR445, BR-86057970 Londrina, Parana, Brazil
Sao Leopoldo Mand Inst & Researcher Ctr, Lab Immunol & Mol Biol, Campinas, SP, Brazil
Univ Sao Paulo, Dept Pharmacol, Ribeirao Preto Med Sch, Ave Bandeirantes S-N, BR-14050490 Sao Paulo, Brazil
Sao Paulo State Univ, Dept Environm Engn, Sorocaba, Brazil
Univ Estadual Londrina, Dept Ciencias Farmaceut, Univ Hosp, Ave Robert Koch 60, BR-86038350 Londrina, Parana, Brazil
Sao Paulo State Univ, Dept Environm Engn, Sorocaba, Brazil
FAPESP: 2011/19670-0
FAPESP: 2010/15014-9
FAPESP: 2013/08216-2
Financiadora de Estudos e Projetos and Secretaria de Estado da Ciencia, Tecnologia e Ensino Superior do Parana (FINEP/SETI-PR, Brazil): 01.12.0294.00 (0476/11)
