Phosphoramidon, an endothelin-converting enzyme inhibitor, attenuates lipopolysaccharide-induced acute lung injury

Tapan M. Bhavsar, Joseph M. Cerreta, Ming Liu, Sandra E. Reznik, Jerome O. Cantor

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Phosphoramidon blocks the formation of endothelin-1 (ET-1), a proinflammatory mediator implicated in the pathogenesis of a variety of lung diseases. To determine whether phosphoramidon can ameliorate pulmonary inflammation, our laboratory undertook a series of experiments involving treatment of hamsters with either intraperitoneal (i.p.) or aerosolized phosphoramidon prior to induction of acute lung injury by intratracheal administration of lipopolysaccharide (LPS). The results indicate that phosphoramidon significantly reduces LPS-induced pulmonary inflammation as measured by lung histology, neutrophil content of bronchoalveolar lavage (BAL) fluid, percent tumor necrosis factor receptor 1 (TNFR1)-labeled BAL macrophages, and alveolar septal cell apoptosis. In additional experiments, i.p. administration of a novel endothelin A receptor anatgonist (HJP272) similarly decreased BAL neutrophils, whereas i.p. administration of either ET-1, or its precursor peptide, "big" ET-1, had the opposite effect. These findings support further evaluation of phosphoramidon and other ET-1 suppressors as potential treatments for human inflammatory lung disease.

Original languageEnglish (US)
Pages (from-to)141-154
Number of pages14
JournalExperimental Lung Research
Volume34
Issue number3
DOIs
StatePublished - Mar 1 2008
Externally publishedYes

Fingerprint

Acute Lung Injury
Endothelins
Enzyme Inhibitors
Lipopolysaccharides
Endothelin-1
Pulmonary diseases
Bronchoalveolar Lavage
Lung Diseases
Pneumonia
Neutrophils
Alveolar Epithelial Cells
Endothelin A Receptors
Histology
Macrophages
Tumor Necrosis Factor Receptors
Bronchoalveolar Lavage Fluid
Cricetinae
Experiments
Endothelin-Converting Enzymes
phosphoramidon

Keywords

  • Endothelin
  • Lipopolysaccharide
  • Lung
  • Phosphoramidon

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Phosphoramidon, an endothelin-converting enzyme inhibitor, attenuates lipopolysaccharide-induced acute lung injury. / Bhavsar, Tapan M.; Cerreta, Joseph M.; Liu, Ming; Reznik, Sandra E.; Cantor, Jerome O.

In: Experimental Lung Research, Vol. 34, No. 3, 01.03.2008, p. 141-154.

Research output: Contribution to journalArticle

Bhavsar, Tapan M. ; Cerreta, Joseph M. ; Liu, Ming ; Reznik, Sandra E. ; Cantor, Jerome O. / Phosphoramidon, an endothelin-converting enzyme inhibitor, attenuates lipopolysaccharide-induced acute lung injury. In: Experimental Lung Research. 2008 ; Vol. 34, No. 3. pp. 141-154.
@article{34dd9e75566147c18e442488e63ab7e5,
title = "Phosphoramidon, an endothelin-converting enzyme inhibitor, attenuates lipopolysaccharide-induced acute lung injury",
abstract = "Phosphoramidon blocks the formation of endothelin-1 (ET-1), a proinflammatory mediator implicated in the pathogenesis of a variety of lung diseases. To determine whether phosphoramidon can ameliorate pulmonary inflammation, our laboratory undertook a series of experiments involving treatment of hamsters with either intraperitoneal (i.p.) or aerosolized phosphoramidon prior to induction of acute lung injury by intratracheal administration of lipopolysaccharide (LPS). The results indicate that phosphoramidon significantly reduces LPS-induced pulmonary inflammation as measured by lung histology, neutrophil content of bronchoalveolar lavage (BAL) fluid, percent tumor necrosis factor receptor 1 (TNFR1)-labeled BAL macrophages, and alveolar septal cell apoptosis. In additional experiments, i.p. administration of a novel endothelin A receptor anatgonist (HJP272) similarly decreased BAL neutrophils, whereas i.p. administration of either ET-1, or its precursor peptide, {"}big{"} ET-1, had the opposite effect. These findings support further evaluation of phosphoramidon and other ET-1 suppressors as potential treatments for human inflammatory lung disease.",
keywords = "Endothelin, Lipopolysaccharide, Lung, Phosphoramidon",
author = "Bhavsar, {Tapan M.} and Cerreta, {Joseph M.} and Ming Liu and Reznik, {Sandra E.} and Cantor, {Jerome O.}",
year = "2008",
month = "3",
day = "1",
doi = "10.1080/01902140701884430",
language = "English (US)",
volume = "34",
pages = "141--154",
journal = "Experimental Lung Research",
issn = "0190-2148",
publisher = "Informa Healthcare",
number = "3",

}

TY - JOUR

T1 - Phosphoramidon, an endothelin-converting enzyme inhibitor, attenuates lipopolysaccharide-induced acute lung injury

AU - Bhavsar, Tapan M.

AU - Cerreta, Joseph M.

AU - Liu, Ming

AU - Reznik, Sandra E.

AU - Cantor, Jerome O.

PY - 2008/3/1

Y1 - 2008/3/1

N2 - Phosphoramidon blocks the formation of endothelin-1 (ET-1), a proinflammatory mediator implicated in the pathogenesis of a variety of lung diseases. To determine whether phosphoramidon can ameliorate pulmonary inflammation, our laboratory undertook a series of experiments involving treatment of hamsters with either intraperitoneal (i.p.) or aerosolized phosphoramidon prior to induction of acute lung injury by intratracheal administration of lipopolysaccharide (LPS). The results indicate that phosphoramidon significantly reduces LPS-induced pulmonary inflammation as measured by lung histology, neutrophil content of bronchoalveolar lavage (BAL) fluid, percent tumor necrosis factor receptor 1 (TNFR1)-labeled BAL macrophages, and alveolar septal cell apoptosis. In additional experiments, i.p. administration of a novel endothelin A receptor anatgonist (HJP272) similarly decreased BAL neutrophils, whereas i.p. administration of either ET-1, or its precursor peptide, "big" ET-1, had the opposite effect. These findings support further evaluation of phosphoramidon and other ET-1 suppressors as potential treatments for human inflammatory lung disease.

AB - Phosphoramidon blocks the formation of endothelin-1 (ET-1), a proinflammatory mediator implicated in the pathogenesis of a variety of lung diseases. To determine whether phosphoramidon can ameliorate pulmonary inflammation, our laboratory undertook a series of experiments involving treatment of hamsters with either intraperitoneal (i.p.) or aerosolized phosphoramidon prior to induction of acute lung injury by intratracheal administration of lipopolysaccharide (LPS). The results indicate that phosphoramidon significantly reduces LPS-induced pulmonary inflammation as measured by lung histology, neutrophil content of bronchoalveolar lavage (BAL) fluid, percent tumor necrosis factor receptor 1 (TNFR1)-labeled BAL macrophages, and alveolar septal cell apoptosis. In additional experiments, i.p. administration of a novel endothelin A receptor anatgonist (HJP272) similarly decreased BAL neutrophils, whereas i.p. administration of either ET-1, or its precursor peptide, "big" ET-1, had the opposite effect. These findings support further evaluation of phosphoramidon and other ET-1 suppressors as potential treatments for human inflammatory lung disease.

KW - Endothelin

KW - Lipopolysaccharide

KW - Lung

KW - Phosphoramidon

UR - http://www.scopus.com/inward/record.url?scp=39849084620&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=39849084620&partnerID=8YFLogxK

U2 - 10.1080/01902140701884430

DO - 10.1080/01902140701884430

M3 - Article

C2 - 18307123

AN - SCOPUS:39849084620

VL - 34

SP - 141

EP - 154

JO - Experimental Lung Research

JF - Experimental Lung Research

SN - 0190-2148

IS - 3

ER -