Document Detail

Effects of ONO-1078, a peptide leukotriene antagonist, on endotoxin-induced acute lung injury.
MedLine Citation:
PMID:  7952560     Owner:  NLM     Status:  MEDLINE    
The role of lipoxygenase metabolites in the pathogenesis of endotoxin (LPS)-induced lung injury remains to be clarified. We investigated the contribution of peptide leukotrienes to LPS-induced acute lung injury using a potent antagonist, ONO-1078 (ONO). Experimental groups consisted of a saline group (n = 10), an LPS group (n = 9) injected intravenously with 2 mg E. coli LPS, an ONO group (n = 8) receiving 30 mg/kg of intraperitoneal ONO, and an LPS+ONO group (n = 6) receiving 30 mg/kg of ONO intraperitoneally 10 min before the LPS injection. The [125I]albumin lung plasma ratio, which is a parameter of acute lung injury, was significantly increased (p < 0.01) in the LPS group compared with the saline, ONO, and LPS+ONO groups. The [125I]albumin BAL fluid plasma ratio was also increased (p < 0.01) in the LPS group compared with the other groups. ONO pretreatment attenuated the LPS-induced increases in neutrophil counts in the BAL fluid. In vitro studies showed that ONO suppresses the neutrophil chemotaxis induced by LTB4, zymosan-activated serum, and FMLP. We conclude that (1) ONO-1078 attenuates LPS-induced acute lung injury; and (2) this effect appears mainly a result of its potent antagonistic actions against peptide leukotrienes and also, in part, the suppression of neutrophil chemotaxis.
A Ishizaka; N Hasegawa; F Sakamaki; S Tasaka; H Nakamura; K Kishikawa; A Yamada; T Obata; K Sayama; T Urano
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  American journal of respiratory and critical care medicine     Volume:  150     ISSN:  1073-449X     ISO Abbreviation:  Am. J. Respir. Crit. Care Med.     Publication Date:  1994 Nov 
Date Detail:
Created Date:  1994-12-13     Completed Date:  1994-12-13     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  9421642     Medline TA:  Am J Respir Crit Care Med     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1325-31     Citation Subset:  AIM; IM    
Department of Medicine, School of Medicine, Keio University, Japan.
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MeSH Terms
Albumins / metabolism
Bronchoalveolar Lavage Fluid / cytology
Chemotaxis, Leukocyte
Chromones / pharmacology*
Escherichia coli
Guinea Pigs
Leukocyte Count
Lung / pathology
Muramidase / metabolism
Neutrophils / metabolism
Organ Size
Respiratory Distress Syndrome, Adult / chemically induced,  pathology,  physiopathology*
SRS-A / antagonists & inhibitors*
Superoxides / metabolism
Reg. No./Substance:
0/Albumins; 0/Chromones; 0/Endotoxins; 0/Lipopolysaccharides; 0/SRS-A; 0/pranlukast; 11062-77-4/Superoxides; EC

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