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

Autor: Staurengo-Ferrari L; Departamento de Patologia, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Rod. Celso Garcia Cid KM480 PR445, Cx Postal 10011, CEP 86057-970 Londrina, Paraná, Brazil., Ruiz-Miyazawa KW; Departamento de Patologia, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Rod. Celso Garcia Cid KM480 PR445, Cx Postal 10011, CEP 86057-970 Londrina, Paraná, Brazil., Pinho-Ribeiro FA; Departamento de Patologia, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Rod. Celso Garcia Cid KM480 PR445, Cx Postal 10011, CEP 86057-970 Londrina, Paraná, Brazil., Domiciano TP; Departamento de Patologia, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Rod. Celso Garcia Cid KM480 PR445, Cx Postal 10011, CEP 86057-970 Londrina, Paraná, Brazil., Fattori V; Departamento de Patologia, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Rod. Celso Garcia Cid KM480 PR445, Cx Postal 10011, CEP 86057-970 Londrina, Paraná, Brazil., Mizokami SS; Departamento de Patologia, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Rod. Celso Garcia Cid KM480 PR445, Cx Postal 10011, CEP 86057-970 Londrina, Paraná, Brazil., Pelayo JS; Departamento de Microbiologia, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Rod. Celso Garcia Cid KM480 PR445, Cx Postal 10011, CEP 86057-970 Londrina, Paraná, Brazil., Bordignon J; Laboratorio de Virologia Molecular, Instituto Carlos Chagas, FIOCRUZ, CEP 81350-010 Curitiba, Paraná, Brazil., Figueiredo F; Laboratory of Pathology, Faculty of Medicine, University of Brasilia, CEP 70910-900 Brasilia, Brazil., Casagrande R; Department of Pharmaceutical Sciences, Healthy Sciences Centre, Londrina State University, Av. Robert Koch, 60, CEP 86038-350 Londrina, Paraná, Brazil., Miranda KM; Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, USA., Verri WA Jr; Departamento de Patologia, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Rod. Celso Garcia Cid KM480 PR445, Cx Postal 10011, CEP 86057-970 Londrina, Paraná, Brazil. Electronic address: waverri@uel.br.
Jazyk: angličtina
Zdroj: Free radical biology & medicine [Free Radic Biol Med] 2017 Jul; Vol. 108, pp. 487-499. Date of Electronic Publication: 2017 Apr 15.
DOI: 10.1016/j.freeradbiomed.2017.04.016
Abstrakt: 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.
(Copyright © 2017 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE