The nitroxyl donor Angeli's salt ameliorates Staphylococcus aureus-induced septic arthritis in mice

作者：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 Florencio; Casagrande Rubia; Miranda Katrina M; Verri Waldiceu A Jr^*

来源：Free Radical Biology and Medicine, 2017, 108: 487-499.

DOI：10.1016/j.freeradbiomed.2017.04.016

• Nitroxyl
• Angeli's salt
• Septic arthritis
• Pain
• Leukocytes
• Cytokines
• Oxidative stress
• Nitric oxide

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-kappa B 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.

• 出版日期2017-7