The nitroxyl donor Angeli's salt ameliorates Staphylococcus aureus-induced septic arthritis in mice
Ruiz-Miyazawa, Kenji W
Pinho-Ribeiro, Felipe A
Domiciano, Talita P
Mizokami, Sandra S
Pelayo, Jacinta S
Miranda, Katrina M
Verri, Waldiceu A
AffiliationUniv Arizona, Dept Chem & Biochem
MetadataShow full item record
PublisherELSEVIER SCIENCE INC
CitationStaurengo-Ferrari, L., Ruiz-Miyazawa, K. W., Pinho-Ribeiro, F. A., Domiciano, T. P., Fattori, V., Mizokami, S. S., ... & Miranda, K. M. (2017). The nitroxyl donor Angeli's salt ameliorates Staphylococcus aureus-induced septic arthritis in mice. Free Radical Biology and Medicine, 108, 487-499.
Rights© 2017 Elsevier Inc. All rights reserved.
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AbstractSeptic arthritis is a severe and rapidly debilitating disease associated with severe joint pain, inflammation and oxidative stress. Nitroxyl (HNO) has become a nitrogen oxide of significant interest due to its pharmacological endpoints that are potentially favorable for treating varied diseases. However, whether HNO also serves as a treatment to septic arthritis is currently unknown. The aim of this study was to investigate the effect of the HNO donor, Angeli's salt (AS), in the outcome of chronic Staphylococcus aureus (S. aureus)-induced septic arthritis in mice. Daily treatment with AS inhibited mechanical hyperalgesia and inflammation (edema, leukocyte migration, cytokines release and NF-κB activation, and oxidative stress) resulting in reduced disease severity (clinical course, histopathological changes, proteoglycan levels in the joints, and osteoclastogenesis). In addition, AS decreased the number of S. aureus colony forming unities in synovial tissue, enhanced the bactericidal effect of macrophages and inhibited the worsening of systemic inflammatory response (leukocyte counts in the lung and systemic proinflammatory cytokine concentration). Our results suggest for the first time the therapeutic potential of AS in a model of septic arthritis by mechanisms involving microbicidal effects, anti-inflammatory actions and reduction of disease severity.
Note12 month embargo; available online 15 April 2017
VersionFinal accepted manuscript
SponsorsCNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico); MCTI/SETI/Fundacao Araucaria (Ministerio da Ciencia, Tecnologia e Inovacao/Secretaria da Ciencia, Tecnologia, e Ensino Superior do Parana/Fundacao Araucaria); Decit/SCTIE/MS (Departamento de Ciencia e Tecnologia da Secretaria de Ciencia, Tecnologia e Insumos Estrategicos, Ministerio da Saude); Fundacao Araucaria; Coordenadoria de Aperfeicoamento de Pessoal de Nivel Superior (CAPES); INCT (National Institutes of Science and Technology) - MCTI/CNPq/CAPES/Fundacao Araucaria, Brazil; CAPES [PDSE - 99999.007507/2014-03]; CNPq [161279/2015-5]; CAPES/Fundacao Araucaria; CAPES