Document Detail

Paraquat-induced lung injury: prevention by N-tert-butyl-alpha-phenylnitrone, a free-radical spin-trapping agent.
MedLine Citation:
PMID:  1311515     Owner:  NLM     Status:  MEDLINE    
The herbicide paraquat causes lung injury that is believed to be oxygen-radical mediated. To further characterize this injury and explore new methods of preventing it, we used the spin-trapping agent N-tert-butyl-alpha-phenylnitrone (PBN) to identify the paraquat radical in lung tissue and to reduce the injury resulting from the subsequent generation of reactive oxygen species. The formation of a paraquat free radical by guinea pig lung was detected under anaerobic conditions by electron paramagnetic resonance spectrometry. Infused (25, 50, or 100 mg/kg) into guinea pig lungs (perfused at constant flow with Krebs solution containing 4% bovine serum albumin and ventilated with 95% O2-5% CO2), paraquat produced dose-dependent increases in peak airway pressure (Paw), mean pulmonary arterial perfusion pressure (Ppa), and wet-to-dry (W/D) lung weight ratio. At 100 mg/kg, paraquat increased Paw by 589.6 +/- 59.8% (mean +/- SE, n = 8) and W/D ratio from 5.33 +/- 0.07 to 6.29 +/- 0.11 (P less than 0.001). Pulmonary vascular leak index increased from 0.40 +/- 0.09 to 1.96 +/- 0.45 (P less than 0.02), without changes in pulmonary microvascular pressure. Perfusate concentrations of thromboxane B2 and 6-ketoprostaglandin F1 alpha increased, but indomethacin did not reduce the injury. PBN (2.3 mM) markedly attenuated all evidence of lung injury, which was also reduced by catalase, mannitol, ethanol, and vitamin E.(ABSTRACT TRUNCATED AT 250 WORDS)
T Sata; E Kubota; H P Misra; M Mojarad; H Pakbaz; S I Said
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The American journal of physiology     Volume:  262     ISSN:  0002-9513     ISO Abbreviation:  Am. J. Physiol.     Publication Date:  1992 Feb 
Date Detail:
Created Date:  1992-03-31     Completed Date:  1992-03-31     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0370511     Medline TA:  Am J Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  L147-52     Citation Subset:  IM    
Department of Medicine, University of Illinois, Chicago College of Medicine.
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MeSH Terms
6-Ketoprostaglandin F1 alpha / metabolism
Cyclic N-Oxides
Electron Spin Resonance Spectroscopy
Free Radical Scavengers
Guinea Pigs
Hemodynamics / drug effects
Lung / drug effects*
Microcirculation / drug effects
Nitrogen Oxides / pharmacology*
Paraquat / antagonists & inhibitors,  pharmacology*
Pulmonary Circulation / drug effects
Respiratory Physiological Phenomena
Respiratory System / drug effects
Spin Labels
Thromboxane B2 / metabolism
Grant Support
Reg. No./Substance:
0/Cyclic N-Oxides; 0/Free Radical Scavengers; 0/Nitrogen Oxides; 0/Spin Labels; 3376-24-7/phenyl-N-tert-butylnitrone; 4685-14-7/Paraquat; 54397-85-2/Thromboxane B2; 58962-34-8/6-Ketoprostaglandin F1 alpha

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