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). Pulmona...