Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 487-499 |
| Number of pages | 13 |
| Journal | Free Radical Biology and Medicine |
| Volume | 108 |
| DOIs | |
| State | Published - Jul 1 2017 |
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Keywords
- Angeli's salt
- Cytokines
- Leukocytes
- Nitric oxide
- Nitroxyl
- Oxidative stress
- Pain
- Septic arthritis
ASJC Scopus subject areas
- Biochemistry
- Physiology (medical)
Cite this
The nitroxyl donor Angeli's salt ameliorates Staphylococcus aureus-induced septic arthritis in mice. / Staurengo-Ferrari, Larissa; Ruiz-Miyazawa, Kenji W.; Pinho-Ribeiro, Felipe A.; Domiciano, Talita P.; Fattori, Victor; Mizokami, Sandra S.; Pelayo, Jacinta S.; Bordignon, Juliano; Figueiredo, Florêncio; Casagrande, Rubia; Miranda, Katrina M; Verri, Waldiceu A.
In: Free Radical Biology and Medicine, Vol. 108, 01.07.2017, p. 487-499.Research output: Contribution to journal › Article
}
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.
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
UR - http://www.scopus.com/inward/record.url?scp=85018478376&partnerID=8YFLogxK
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
VL - 108
SP - 487
EP - 499
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
SN - 0891-5849
ER -