PMID- 17510494
OWN - NLM
STAT- MEDLINE
DCOM- 20070718
LR  - 20191110
IS  - 0388-6107 (Print)
IS  - 0388-6107 (Linking)
VI  - 28
IP  - 2
DP  - 2007 Apr
TI  - An inhaled inducible nitric oxide synthase inhibitor reduces damage of 
      Candida-induced acute lung injury.
PG  - 91-9
AB  - 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 N(G)-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-alpha (TNF-alpha) and 
      interleukin-1beta (IL-1beta) 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.
FAU - Ohsugi, Shuji
AU  - Ohsugi S
AD  - Department of Respiratory Medicine, Graduate School of Medical Science, Kyoto 
      Prefectural University of Medicine, Kyoto, Japan.
FAU - Iwasaki, Yoshinobu
AU  - Iwasaki Y
FAU - Takemura, Yoshizumi
AU  - Takemura Y
FAU - Nagata, Kazuhiro
AU  - Nagata K
FAU - Harada, Hidehiko
AU  - Harada H
FAU - Yokomura, Ichiro
AU  - Yokomura I
FAU - Hosogi, Shigekuni
AU  - Hosogi S
FAU - Yuba, Tatsuya
AU  - Yuba T
FAU - Niisato, Naomi
AU  - Niisato N
FAU - Miyazaki, Hiroaki
AU  - Miyazaki H
FAU - Matsubara, Hiroaki
AU  - Matsubara H
FAU - Fushiki, Shinji
AU  - Fushiki S
FAU - Marunaka, Yoshinori
AU  - Marunaka Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Japan
TA  - Biomed Res
JT  - Biomedical research (Tokyo, Japan)
JID - 8100317
RN  - 0 (7-chloro-3-imino-5-methyl-2-azabicyclo(4.1.0)heptane)
RN  - 0 (Amidines)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Heterocyclic Compounds, 2-Ring)
RN  - 14691-52-2 (Peroxynitrous Acid)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
SB  - IM
MH  - Administration, Inhalation
MH  - Amidines/pharmacology
MH  - Animals
MH  - Bronchoalveolar Lavage Fluid
MH  - Candidiasis/*drug therapy
MH  - Enzyme Inhibitors/*administration & dosage/*pharmacology
MH  - Heterocyclic Compounds, 2-Ring/pharmacology
MH  - Humans
MH  - Lung Diseases/*microbiology
MH  - *Lung Injury
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Nitric Oxide/chemistry
MH  - Nitric Oxide Synthase/*antagonists & inhibitors
MH  - Oxidative Stress
MH  - Peroxynitrous Acid/chemistry
EDAT- 2007/05/19 09:00
MHDA- 2007/07/19 09:00
CRDT- 2007/05/19 09:00
PHST- 2007/05/19 09:00 [pubmed]
PHST- 2007/07/19 09:00 [medline]
PHST- 2007/05/19 09:00 [entrez]
AID - JST.JSTAGE/biomedres/28.91 [pii]
AID - 10.2220/biomedres.28.91 [doi]
PST - ppublish
SO  - Biomed Res. 2007 Apr;28(2):91-9. doi: 10.2220/biomedres.28.91.