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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Authors | Sung Kyoung Kim, Seung Joon Rho, Seung Hoon Kim, Shin Young Kim, So Hyang Song, Jin Young Yoo, Chi Hong Kim, Sang Haak Lee |
Journal | Clinical and experimental pharmacology & physiology
(Clin Exp Pharmacol Physiol)
Vol. 46
Issue 2
Pg. 153-162
(02 2019)
ISSN: 1440-1681 [Electronic] Australia |
PMID | 30403294
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2018 John Wiley & Sons Australia, Ltd. |
Chemical References |
- Cytokines
- Enzyme Inhibitors
- Lipopolysaccharides
- NF-kappa B
- Onium Compounds
- diphenyleneiodonium
- Peroxidase
- Nitric Oxide Synthase Type II
- NADPH Oxidases
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Topics |
- Acute Lung Injury
(chemically induced, metabolism, pathology, prevention & control)
- Animals
- Cytokines
(metabolism)
- Enzyme Activation
(drug effects)
- Enzyme Inhibitors
(pharmacology)
- Gene Expression Regulation, Enzymologic
(drug effects)
- Lipopolysaccharides
(pharmacology)
- Lung
(drug effects, metabolism, pathology)
- MAP Kinase Signaling System
(drug effects)
- Male
- NADPH Oxidases
(antagonists & inhibitors, metabolism)
- NF-kappa B
(metabolism)
- Nitric Oxide Synthase Type II
(metabolism)
- Onium Compounds
(pharmacology)
- Oxidative Stress
(drug effects)
- Peroxidase
(metabolism)
- Rats
- Rats, Sprague-Dawley
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