GLUTATHIONE STATUS OF ISOLATED RABBIT LUNGS - EFFECTS OF NITROFURANTOIN AND PARAQUAT PERFUSION WITH NORMOXIC AND HYPEROXIC VENTILATION

Thirty-min perfusion of isolated rabbit lungs with a Krebs-Ringer bicarbonate buffer containing 420 .mu.M paraquat (PQ) or nitrofurantoin (NF) resulted in increases in lung oxidized glutathione (GSSG) content of 589 and 2656%, respectively, over control levels. The degree of glutathione efflux was also increased with both agents, i.e., 77 and 238% above control leakage for PQ and NF, respectively. The pulmonary toxicity of both compounds is heightened by conditions of hyperoxia (O2). Ventilation of lungs with 95% O2-5% CO2 did not, in itself, significantly alter glutathione efflux, GSH or GSSG levels. Ventilation with 95% O2-5% CO2 increased lung GSSG levels in PQ-perfused lungs 225% over PQ-air-perfused lungs, a combined effect not observed with NF-O2, wherein mean GSSG levels were only 72% of that observed with NF-air. Glutathione efflux in PQ-O2-treated lungs declined somewhat (20%) compared to that observed with PQ-air, but a significant increase in the amount of glutathione efflux was seen with NF-O2-treated lungs, i.e., 120 and 310%, respectively, over that attributable to NF or O2 alone. Although the biochemical mechanisms of toxicity of these compounds are thought to be very similar, the disparate degree of GSH oxidation observed with equimolar levels of PQ and NF may indicate differences in reactivity towards glutathione and other lung sulfhydryl pools. The stimulation of the oxidative effects of PQ and NF on lung GSH due to hyperoxic ventilation may be related to the reported O2 enhancement of their toxicity.