Critical Care |

Antiinflammatory Effects of Diphenyleneiodonium in Lipopolysaccharide-Induced Acute Lung Injury in Rats FREE TO VIEW

Sung-Kyoung Kim, MD; Ki Hoon Park, MD; Yu Mi Ko, MD; Hyun Hui Kang, MD; Ju Sang Kim, MD; Sang Haak Lee, MD; So Hyang Song, MD; Jinyoung Yoo, MD; Chi Hong Kim, MD
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Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea (the Republic of)

Chest. 2015;148(4_MeetingAbstracts):179A. doi:10.1378/chest.2272210
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SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 28, 2015 at 01:30 PM - 02:30 PM

PURPOSE: NADPH oxidase (NOX) plays an important role in inflammatory responses by producing reactive oxygen species and the inhibition of NOX has been shown to participate in anti-inflammatory action in some inflammatory 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) model.

METHODS: Sprague Dawley rats were intraperitoneally administered DPI (5 mg/kg) 30 minutes after intratracheal instillation with LPS (3 mg/kg). After 6 hours, bronchoalveolar lavage fluid (BALF) and lung tissue were collected. The numbers of inflammatory cells and cytokine release (TNF-α, IL-1β, and IL-6) in BALF were detected by cell counting and ELISA. In lung tissues, NF-κB and myeloperoxidase (MPO) activity and ALI score were measured. Inducible nitric oxide synthase (iNOS) was examined by immunohistochemistry. To identify the anti-inflammatory mechanism of DPI, activation of MAPK and NF-κB pathways was measured by western blot analysis.

RESULTS: DPI-treated rats showed significantly reduced numbers of inflammatory cells, production of inflammatory cytokines (TNF-α, IL-1β and IL-6) in BALF compared to LPS-treated rats. In lung tissues, NF-κB and MPO activity, ALI scores, and iNOS expression were significantly decreased in DPI-treated rats compared to LPS-treated rats. Western blot analysis demonstrated that DPI significantly suppressed LPS-induced activation of MAPK and NF-κB pathways.

CONCLUSIONS: Our results suggest that DPI may have an anti-inflammatory effect on LPS-induced ALI via suppression of the activation of MAPK and NF-κB pathways.

CLINICAL IMPLICATIONS: DPI could be a useful therapeutic agent of ALI treatment.

DISCLOSURE: The following authors have nothing to disclose: Sung-Kyoung Kim, Ki Hoon Park, Yu Mi Ko, Hyun Hui Kang, Ju Sang Kim, Sang Haak Lee, So Hyang Song, Jinyoung Yoo, Chi Hong Kim

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