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Staurengo-Ferrari, Larissa ^[1] ; Ruiz-Miyazawa, Kenji W. ^[1] ; Pinho-Ribeiro, Felipe A. ^[1] ; Fattori, Victor ^[1] ; Zaninelli, Tiago H. ^[1] ; Badaro-Garcia, Stephanie ^[1] ; Borghi, Sergio M. ^[1] ; Carvalho, Thacyana T. ^[1] ; Alves-Filho, Jose C. ^[2] ; Cunha, Thiago M. ^[2] ; Cunha, Fernando Q. ^[2] ; Casagrande, Rubia ^[3] ; Verri Jr, Waldiceu A.

Afiliação do(s) autor(es)

^[1] Univ Estadual Londrina, Dept Ciencias Patol, Londrina - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Pharmacol, Ribeirao Preto - Brazil

^[3] Univ Estadual Londrina, Dept Ciencias Farmaceut, Londrina - Brazil

• Tipo de documento: Artigo Científico
• Fonte: FRONTIERS IN PHARMACOLOGY; v. 9, OCT 2 2018.
• Citações Web of Science: 5

Resumo

Gouty arthritis is characterized by an intense inflammatory response to monosodium urate crystals (MSU), which induces severe pain and reduction in the life quality of patients. Trans-Chalcone (1,3-diphenyl-2-propen-1-one) is a flavonoid precursor presenting biological activities such as anti-inflammatory and antioxidant proprieties. Thus, the aim of this work was to evaluate the protective effects of trans-Chalcone in experimental gout arthritis in mice. Mice were treated with trans-Chalcone (3, 10, or 30 mg/kg, per oral) or vehicle (Tween 80 20% plus saline) 30 min before intra-articular injection of MSU (100 mu g/knee joint, intra-articular). We observed that trans-Chalcone inhibited MSU-induced mechanical hyperalgesia, edema, and leukocyte recruitment (total leukocytes, neutrophils, and mononuclear cells) in a dose-dependent manner. Trans-Chalcone also decreased inflammatory cell recruitment as observed in Hematoxylin and Eosin (HE) staining and the intensity of fluorescence of LysM-eGFP+ cells in the confocal microscopy. Trans-Chalcone reduced MSU-induced oxidative stress as observed by an increase in the antioxidant defense {[}Glutathione (GSH), Ferric Reducing (FRAP), and 2,2'-Azinobis-3-ethylbenzothiazoline 6-sulfonic acid (ABTS assays)] and reduction in reactive oxygen and nitrogen species production {[}superoxide anion (NBT assay) and nitrite (NO assay)]. Furthermore, it reduced in vivo MSU-induced interleukin-1 beta (1L-1 beta), Tumor necrosis factor-alpha (INF-alpha), and IL-6 production, and increased Transforming growth factor-beta (TGF-beta) production. Importantly, trans-Chalcone reduced nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B) activation and thereby the mRNA expression of the inflammasome components Nlrp3 (cryopyrin), Asc (apoptosis-associated speck-like protein containing a CARD), Pro-caspase-1 and Pro-IL-1 beta. In vitro, trans-Chalcone reduced the MSU-induced release of IL-1 beta in lipopolysaccharide (LPS)-primed macrophages. Therefore, the pharmacological effects of trans-Chalcone indicate its therapeutic potential as an analgesic and anti-inflammatory flavonoid for the treatment of gout. (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: 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