TY - JOUR
T1 - The nitroxyl donor Angeli's salt ameliorates Staphylococcus aureus-induced septic arthritis in mice
AU - Staurengo-Ferrari, Larissa
AU - Ruiz-Miyazawa, Kenji W.
AU - Pinho-Ribeiro, Felipe A.
AU - Domiciano, Talita P.
AU - Fattori, Victor
AU - Mizokami, Sandra S.
AU - Pelayo, Jacinta S.
AU - Bordignon, Juliano
AU - Figueiredo, Florêncio
AU - Casagrande, Rubia
AU - Miranda, Katrina M.
AU - Verri, Waldiceu A.
N1 - Funding Information:
This work was supported by grants from CNPq (Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico), MCTI/SETI/Funda??o Arauc?ria (Minist?rio da Ci?ncia, Tecnologia e Inova??o/Secretaria da Ci?ncia, Tecnologia, e Ensino Superior do Paran?/Funda??o Arauc?ria), Decit/SCTIE/MS (Departamento de Ci?ncia e Tecnologia da Secretaria de Ci?ncia, Tecnologia e Insumos Estrat?gicos, Minist?rio da Sa?de) Intermediated by CNPq and support of Funda??o Arauc?ria, Coordenadoria de Aperfei?oamento de Pessoal de N?vel Superior (CAPES), INCT (National Institutes of Science and Technology) ? MCTI/CNPq/CAPES/Funda??o Arauc?ria, Brazil. LSF received a scholarship from CAPES during her Ph.D. and to conduct sandwich Ph.D. at University of Arizona (Process: PDSE ? 99999.007507/2014-03), and received a CNPq post-doctoral fellowship (Process: 161279/2015-5). TPD received a post-doctoral fellowship from CAPES/Funda??o Arauc?ria. KWR-M, FAP-R, VF and SSM received Ph.D. fellowship from CAPES.
PY - 2017/7/1
Y1 - 2017/7/1
N2 - Septic 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.
AB - Septic 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.
KW - Angeli's salt
KW - Cytokines
KW - Leukocytes
KW - Nitric oxide
KW - Nitroxyl
KW - Oxidative stress
KW - Pain
KW - Septic arthritis
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UR - http://www.scopus.com/inward/citedby.url?scp=85018478376&partnerID=8YFLogxK
U2 - 10.1016/j.freeradbiomed.2017.04.016
DO - 10.1016/j.freeradbiomed.2017.04.016
M3 - Article
C2 - 28419865
AN - SCOPUS:85018478376
VL - 108
SP - 487
EP - 499
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
SN - 0891-5849
ER -