15d-PGJ(2)-loaded nanocapsules ameliorate experimental gout arthritis by reducing pain and inflammation in a PPAR-gamma-sensitive manner in mice

Autor(es):Mostrar menos -

Ruiz-Miyazawa, Kenji W. ^[1] ; Staurengo-Ferrari, Larissa ^[1] ; Pinho-Ribeiro, Felipe A. ^[1] ; Fattori, Victor ^[1] ; Zaninelli, Tiago H. ^[1] ; Badaro-Garcia, Stephanie ^[1] ; Borghi, Sergio M. ^[1] ; Andrade, Ketlem C. ^[1] ; Clemente-Napimoga, Juliana T. ^[2] ; Alves-Filho, Jose C. ^[3] ; Cunha, Thiago M. ^[3] ; Fraceto, Leonardo F. ^[4] ; Cunha, Fernando Q. ^[3] ; Napimoga, Marcelo H. ^[2] ; Casagrande, Rubia ^[5] ; Verri, Jr., Waldiceu A. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Estadual Londrina, Dept Ciencias Patol, Rod Celso Garcia Cid, Km 380, PR445, BR-86057970 Londrina, Parana - Brazil

^[2] Sao Leopoldo Mand Inst & Researcher Ctr, Lab Immunol & Mol Biol, Campinas, SP - Brazil

^[3] Univ Sao Paulo, Dept Pharmacol, Ribeirao Preto Med Sch, Ave Bandeirantes S-N, BR-14050490 Sao Paulo - Brazil

^[4] Sao Paulo State Univ, Dept Environm Engn, Sorocaba - Brazil

^[5] Univ Estadual Londrina, Dept Ciencias Farmaceut, Univ Hosp, Ave Robert Koch 60, BR-86038350 Londrina, Parana - Brazil

• Tipo de documento: Artigo Científico
• Fonte: SCIENTIFIC REPORTS; v. 8, SEP 18 2018.
• Citações Web of Science: 8

Resumo

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. (AU)

• Processo FAPESP: 13/08216-2 - CPDI - Centro de Pesquisa em Doenças Inflamatórias
• Beneficiário: Fernando de Queiroz Cunha
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 10/15014-9 - Avaliação do efeito imunofarmacológico da 15d-PGJ2 complexada a nanopartículas poliméricas biodegradáveis no controle da evolução da doença periodontal experimental
• Beneficiário: Marcelo Henrique Napimoga
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 11/19670-0 - Mecanismos envolvidos na fisiopatologia da artrite reumatóide, dor e sepse
• Beneficiário: Fernando de Queiroz Cunha
• Modalidade de apoio: Auxílio à Pesquisa - Temático