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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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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]
Total Authors: 16
[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
Total Affiliations: 5
Document type: Journal article
Source: SCIENTIFIC REPORTS; v. 8, SEP 18 2018.
Web of Science Citations: 5

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)

FAPESP's process: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases
Grantee:Fernando de Queiroz Cunha
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 11/19670-0 - Mechanisms involved in the pathophysiology of rheumatoid arthritis, pain and sepsis
Grantee:Fernando de Queiroz Cunha
Support type: Research Projects - Thematic Grants
FAPESP's process: 10/15014-9 - Evaluation of the effect of 15d-PGJ2-loaded on polymeric biodegradable nanoparticles to control the evolution of the experimental periodontal disease
Grantee:Marcelo Henrique Napimoga
Support type: Regular Research Grants