15d-PGJ2-loaded nanocapsules ameliorate experimental gout arthritis by reducing pain and inflammation in a PPAR-gamma-sensitive manner in mice.

Abstract

Gout arthritis (GA) is a painful inflammatory disease in response to monosodium urate (MSU) crystals in the joints. 15deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) is a natural activator of PPAR-γ with analgesic, anti-inflammatory, and pro-resolution properties. Thus, we aimed to evaluate the effect and mechanisms of action of 15d-PGJ2 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-PGJ2-loaded NC, inert NC, free 15d-PGJ2 (without NC), or 15d-PGJ2-loaded NC+ GW9662, a PPAR-γ inhibitor. We show that 15d-PGJ2-loaded NC provided analgesic effect in a dose that the free 15d-PGJ2 failed to inhibiting pain and inflammation. Hence, 15d-PGJ2-loaded NC reduced MSU-induced IL-1β, TNF-α, IL-6, IL-17, and IL-33 release and oxidative stress. Also, 15d-PGJ2-loaded NC decreased the maturation of IL-1β in LPS-primed BMDM triggered by MSU. Further, 15d-PGJ2-loaded NC decreased the expression of the components of the inflammasome Nlrp3, Asc, and Pro-caspase-1, as consequence of inhibiting NF-κB activation. All effects were PPAR-γ-sensitive. Therefore, we demonstrated that 15d-PGJ2-loaded NC present analgesic and anti-inflammatory properties in a PPAR-γ-dependent manner inhibiting IL-1β release and NF-κB activation in GA. Concluding, 15d-PGJ2-loaded NC ameliorates MSU-induced GA in a PPAR-γ-sensitive manner.

• Authors: Kenji W Ruiz-Miyazawa, Larissa Staurengo-Ferrari, Felipe A Pinho-Ribeiro, Victor Fattori, Tiago H Zaninelli, Stephanie Badaro-Garcia, Sergio M Borghi, Ketlem C Andrade, Juliana T Clemente-Napimoga, Jose C Alves-Filho, Thiago M Cunha, Leonardo F Fraceto, Fernando Q Cunha, Marcelo H Napimoga, Rubia Casagrande, Waldiceu A Verri Jr
• Journal: Scientific reports (Sci Rep) Vol. 8 Issue 1 Pg. 13979 (09 18 2018) ISSN: 2045-2322 [Electronic] England
• PMID: 30228306 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 15-deoxyprostaglandin J2
• Antioxidants
• Nanocapsules
• PPAR gamma
• Uric Acid
• Prostaglandin D2

Topics

• Animals
• Antioxidants (toxicity)
• Arthritis, Experimental (metabolism, pathology, prevention & control)
• Arthritis, Gouty (metabolism, pathology, prevention & control)
• Inflammation (chemically induced, drug therapy, metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Nanocapsules (administration & dosage)
• Oxidative Stress
• PPAR gamma (metabolism)
• Pain (chemically induced, drug therapy, metabolism)
• Prostaglandin D2 (analogs & derivatives, pharmacology)
• Uric Acid (toxicity)