Paraquat-induced lung injury: prevention by N-tert-butyl-alpha-phenylnitrone, a free-radical spin-trapping agent.
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)
Sata
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Department of Medicine, University of Illinois, Chicago College of Medicine.
Kubota
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Misra
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Mojarad
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Pakbaz
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Said
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D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000818:Animals; D003497:Cyclic N-Oxides; D004578:Electron Spin Resonance Spectroscopy; D016166:Free Radical Scavengers; D006168:Guinea Pigs; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects*; D008833:Microcirculation / Q000187:drug effects; D009589:Nitrogen Oxides / Q000494:pharmacology*; D010269:Paraquat / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011312:Pressure; D011652:Pulmonary Circulation / Q000187:drug effects; D012143:Respiratory Physiological Phenomena; D012137:Respiratory System / Q000187:drug effects; D013113:Spin Labels; D013929:Thromboxane B2 / Q000378:metabolism
D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D009589:Nitrogen Oxides; D013113:Spin Labels; C029217:phenyl-N-tert-butylnitrone; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D010269:Paraquat