Biomedical Research
Online ISSN : 1880-313X
Print ISSN : 0388-6107
ISSN-L : 0388-6107
Full Papers
An inhaled inducible nitric oxide synthase inhibitor reduces damage of Candida-induced acute lung injury
Shuji OHSUGIYoshinobu IWASAKIYoshizumi TAKEMURAKazuhiro NAGATAHidehiko HARADAIchiro YOKOMURAShigekuni HOSOGITatsuya YUBANaomi NIISATOHiroaki MIYAZAKIHiroaki MATSUBARAShinji FUSHIKIYoshinori MARUNAKA
Author information
JOURNAL FREE ACCESS

2007 Volume 28 Issue 2 Pages 91-99

Details
Abstract

Excessive nitric oxide (NO) generated by inducible nitric oxide synthase (iNOS) aggravates acute lung injury (ALI) by producing peroxynitrite. We previously showed by immunostaining that the expression of iNOS was suppressed by inhalation of NG-nitro-L-arginine methyl ester in mice with Candida-induced ALI. This study tested the hypothesis that a novel iNOS inhibitor suppresses not only iNOS expression, but also iNOS messenger RNA (mRNA) production by interrupting a positive feedback loop at the time of NO production in Candida-induced ALI. Mice were pretreated by inhalation of saline or ONO-1714, a selective iNOS inhibitor, and were given an intravenous injection of Candida albicans to induce ALI. After inhalation of 1 mM aerosolized ONO-1714, the nitrite-nitrate concentration in bronchoalveolar lavage fluid (BALF) at 24 h was significantly lower than that after inhalation of saline. Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels and neutrophils in BALF were decreased by inhalation of ONO-1714. Inhalation of ONO-1714 markedly suppressed nitrotyrosine production and inhibited the expression of iNOS mRNA as well as proteins in the lung. Survival was prolonged by inhalation of ONO-1714. We conclude that pretreatment with inhaled ONO-1714 suppresses the production of peroxinitrite and decreases oxidative stress associated with peroxinitrite in Candida-induced ALI.

Information related to the author
© 2007 Biomedical Research Press
Previous article Next article
feedback
Top