Protective effects of diphenyleneiodonium, an NADPH oxidase inhibitor, on lipopolysaccharide-induced acute lung injury.
Clin Exp Pharmacol Physiol
; 46(2): 153-162, 2019 02.
Article
em En
| MEDLINE
| ID: mdl-30403294
ABSTRACT
NADPH oxidase (NOX) plays an important role in inflammatory response by producing reactive oxygen species (ROS). The inhibition of NOX has been shown to induce anti-inflammatory effects in a few experimental models. The aim of this study was to investigate the effects of diphenyleneiodonium (DPI), a NOX inhibitor, on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in a rat model. Sprague-Dawley rats were intraperitoneally administered by DPI (5 mg/kg) 30 minutes after intratracheal instillation of LPS (3 mg/kg). After 6 hours, bronchoalveolar lavage fluid (BALF) and lung tissue were collected. The NOX activity in lung tissue was significantly increased in LPS-treated rats. It was significantly attenuated by DPI. DPI-treated rats showed significant reduction in the intracellular ROS, the number of inflammatory cells, and cytokines (TNF-α and IL-6) in BALF compared with LPS-treated rats. In lung tissue, DPI-treated rats showed significantly decreased malondialdehyde content and increased activity of glutathione peroxidase and superoxide dismutase compared with LPS-treated rats. Lung injury score, myeloperoxidase activity, and inducible nitric oxide synthase expression were significantly decreased in DPI-treated rats compared with LPS-treated animals. Western blotting analysis demonstrated that DPI significantly suppressed LPS-induced activation of NF-κB and ERK1/2 and SAPK/JNK in MAPK pathway. Our results suggest that DPI may have protective effects on LPS-induced ALI thorough anti-oxidative and anti-inflammatory effects which may be due to inactivation of the NF-κB, ERK1/2, and SAPK/JNK pathway. These results suggest the therapeutic potential of DPI as an anti-inflammatory agent in ALI.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oniocompostos
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Lipopolissacarídeos
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NADPH Oxidases
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Inibidores Enzimáticos
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Lesão Pulmonar Aguda
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Clin Exp Pharmacol Physiol
Ano de publicação:
2019
Tipo de documento:
Article