Effect of monocrotaline metabolites on glutathione levels in human and Bovine Pulmonary artery endothelial cells

M. J. Reid, S. K. Dunston, M. W. Lamé, Dennis W Wilson, D. Morin, H. J. Segall

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

After being dehydrogenated by cytochrome P450 enzymes in the liver, monocrotaline's highly-reactive pyrrole metabolite, dehydromonocrotaline, is believed to interact with pulmonary artery endothelial cells to initiate a pulmonary vascular toxicity resembling pulmonary hypertension. Glutathione, an abundant antioxidant in pulmonary artery endothelial cells, has been shown to react with and detoxify the pyrrolic metabolites derived from monocrotaline in the liver. Using high-performance liquid chromatography with electrochemical detection, glutathione levels were measured in a time- and dose-dependent manner in human pulmonary artery endothelial cells following treatment with dehydromonocrotaline, dehydroretronecine and N-ethylmaleimide and bovine pulmonary artery endothelial cells after treatment with dehydromonocrotaline. The bovine cells had 40% less glutathione than the human in the control groups. Bovine pulmonary artery endothelial glutathione levels were depleted 20% more than the human at 15 minutes when treated with 100 μM dehydromonocrotaline. 15μM N-ethylmaleimide caused an 80% depletion of glutathione compared to a 30% depletion with 15μM dehydromonocrotaline in human pulmonary artery endothelial cells.

Original languageEnglish (US)
Pages (from-to)53-68
Number of pages16
JournalResearch Communications in Molecular Pathology and Pharmacology
Volume99
Issue number1
StatePublished - 1998

Fingerprint

Monocrotaline
Pulmonary Artery
Glutathione
Endothelial Cells
Ethylmaleimide
Cytochrome P-450 Enzyme System
Pyrroles
Liver
Pulmonary Hypertension
Blood Vessels
Antioxidants
High Pressure Liquid Chromatography
monocrotaline pyrrole
Lung
Control Groups

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Pathology and Forensic Medicine

Cite this

Effect of monocrotaline metabolites on glutathione levels in human and Bovine Pulmonary artery endothelial cells. / Reid, M. J.; Dunston, S. K.; Lamé, M. W.; Wilson, Dennis W; Morin, D.; Segall, H. J.

In: Research Communications in Molecular Pathology and Pharmacology, Vol. 99, No. 1, 1998, p. 53-68.

Research output: Contribution to journalArticle

@article{47bacd2406c741549f5aa4641072b0fd,
title = "Effect of monocrotaline metabolites on glutathione levels in human and Bovine Pulmonary artery endothelial cells",
abstract = "After being dehydrogenated by cytochrome P450 enzymes in the liver, monocrotaline's highly-reactive pyrrole metabolite, dehydromonocrotaline, is believed to interact with pulmonary artery endothelial cells to initiate a pulmonary vascular toxicity resembling pulmonary hypertension. Glutathione, an abundant antioxidant in pulmonary artery endothelial cells, has been shown to react with and detoxify the pyrrolic metabolites derived from monocrotaline in the liver. Using high-performance liquid chromatography with electrochemical detection, glutathione levels were measured in a time- and dose-dependent manner in human pulmonary artery endothelial cells following treatment with dehydromonocrotaline, dehydroretronecine and N-ethylmaleimide and bovine pulmonary artery endothelial cells after treatment with dehydromonocrotaline. The bovine cells had 40{\%} less glutathione than the human in the control groups. Bovine pulmonary artery endothelial glutathione levels were depleted 20{\%} more than the human at 15 minutes when treated with 100 μM dehydromonocrotaline. 15μM N-ethylmaleimide caused an 80{\%} depletion of glutathione compared to a 30{\%} depletion with 15μM dehydromonocrotaline in human pulmonary artery endothelial cells.",
author = "Reid, {M. J.} and Dunston, {S. K.} and Lam{\'e}, {M. W.} and Wilson, {Dennis W} and D. Morin and Segall, {H. J.}",
year = "1998",
language = "English (US)",
volume = "99",
pages = "53--68",
journal = "Research Communications in Molecular Pathology and Pharmacology",
issn = "1078-0297",
publisher = "PJD Publications Ltd",
number = "1",

}

TY - JOUR

T1 - Effect of monocrotaline metabolites on glutathione levels in human and Bovine Pulmonary artery endothelial cells

AU - Reid, M. J.

AU - Dunston, S. K.

AU - Lamé, M. W.

AU - Wilson, Dennis W

AU - Morin, D.

AU - Segall, H. J.

PY - 1998

Y1 - 1998

N2 - After being dehydrogenated by cytochrome P450 enzymes in the liver, monocrotaline's highly-reactive pyrrole metabolite, dehydromonocrotaline, is believed to interact with pulmonary artery endothelial cells to initiate a pulmonary vascular toxicity resembling pulmonary hypertension. Glutathione, an abundant antioxidant in pulmonary artery endothelial cells, has been shown to react with and detoxify the pyrrolic metabolites derived from monocrotaline in the liver. Using high-performance liquid chromatography with electrochemical detection, glutathione levels were measured in a time- and dose-dependent manner in human pulmonary artery endothelial cells following treatment with dehydromonocrotaline, dehydroretronecine and N-ethylmaleimide and bovine pulmonary artery endothelial cells after treatment with dehydromonocrotaline. The bovine cells had 40% less glutathione than the human in the control groups. Bovine pulmonary artery endothelial glutathione levels were depleted 20% more than the human at 15 minutes when treated with 100 μM dehydromonocrotaline. 15μM N-ethylmaleimide caused an 80% depletion of glutathione compared to a 30% depletion with 15μM dehydromonocrotaline in human pulmonary artery endothelial cells.

AB - After being dehydrogenated by cytochrome P450 enzymes in the liver, monocrotaline's highly-reactive pyrrole metabolite, dehydromonocrotaline, is believed to interact with pulmonary artery endothelial cells to initiate a pulmonary vascular toxicity resembling pulmonary hypertension. Glutathione, an abundant antioxidant in pulmonary artery endothelial cells, has been shown to react with and detoxify the pyrrolic metabolites derived from monocrotaline in the liver. Using high-performance liquid chromatography with electrochemical detection, glutathione levels were measured in a time- and dose-dependent manner in human pulmonary artery endothelial cells following treatment with dehydromonocrotaline, dehydroretronecine and N-ethylmaleimide and bovine pulmonary artery endothelial cells after treatment with dehydromonocrotaline. The bovine cells had 40% less glutathione than the human in the control groups. Bovine pulmonary artery endothelial glutathione levels were depleted 20% more than the human at 15 minutes when treated with 100 μM dehydromonocrotaline. 15μM N-ethylmaleimide caused an 80% depletion of glutathione compared to a 30% depletion with 15μM dehydromonocrotaline in human pulmonary artery endothelial cells.

UR - http://www.scopus.com/inward/record.url?scp=0031912674&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031912674&partnerID=8YFLogxK

M3 - Article

VL - 99

SP - 53

EP - 68

JO - Research Communications in Molecular Pathology and Pharmacology

JF - Research Communications in Molecular Pathology and Pharmacology

SN - 1078-0297

IS - 1

ER -