Characterization of the anti-inflammatory properties of NCX 429, a dual-acting compound releasing nitric oxide and naproxen.
Life Sci
; 126: 28-36, 2015 Apr 01.
Article
em En
| MEDLINE
| ID: mdl-25711428
ABSTRACT
AIMS:
Cyclooxygenase (COX)-inhibiting nitric oxide donors (CINODs) are a new class of drugs that structurally combine a COX inhibitor with a nitric oxide (NO) donating moiety. This combination reduces potential toxicity of the non-steroidal anti-inflammatory drugs (NSAIDs) whilst maintaining the analgesic and anti-inflammatory effects. The present study was undertaken to investigate the anti-inflammatory effects of NCX 429, a naproxen-based CINOD, and to assess the additional properties of NO donation beyond those related to naproxen. MAINMETHODS:
We evaluated the in vitro effects of NCX 429 on oxy-radical production, phagocytosis, cytokine release, MMP-9, PPARγ expression and NF-κB activation in human monocytes/MDM and compared to naproxen. Moreover, we compared the in vivo efficacy of NCX 429 and naproxen in a murine model of peritonitis. KEYFINDINGS:
In all the experiments performed in vitro, NCX 429 reduced the inflammatory responses with equal or higher efficacy compared to naproxen. Moreover, in in vivo experiments, NCX 429, at the lowest dose tested, was able to significantly inhibit cell influx in response to IL-1ß administration although naproxen was found to be more potent than NCX 429 at reducing PGE2 in inflammatory exudates.SIGNIFICANCE:
These results demonstrate that both in vitro and in vivo--in a murine model of peritonitis--NCX 429 elicits significant anti-inflammatory activity, beyond the simple COX inhibition or pure NO release. Therefore, NO donation along with COX inhibition may represent a strategy for investigating inflammatory diseases in which pain and function are not fully resolved by analgesics/anti-inflammatory drugs.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Peritonite
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Anti-Inflamatórios não Esteroides
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Naproxeno
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Doadores de Óxido Nítrico
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Nitratos
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Óxido Nítrico
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Life Sci
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Itália