EFFECTS OF NITROFURANTOIN ON THE GLUTATHIONE REDOX STATUS AND RELATED ENZYMES IN THE ISOLATED, PERFUSED RABBIT LUNG

  • 1 January 1981
    • journal article
    • research article
    • Vol. 34  (3) , 485-492
Abstract
Nitrofurantoin (NF) is a urinary antimicrobial drug which causes pulmonary injury. We measured levels of total lung glutathione (TLG), a tripeptide central to cellular antioxidant defenses and xenobiotic detoxification, and enzyme activities related to maintenance and utilization of reduced glutathione (GSH) in isolated, New Zealand White rabbit lungs perfused with a Kreb''s-Ringer''s bicarbonate medium containing NF (420 .mu.M). After 30 min there was no net difference in the level of TLG [GSH + GSSG(oxidized) + effluent GSH-GSSG] or total nonprotein SH in NF-perfused or control lungs. There was a decrease in the GSH:GSSG redox ratio to 2% of control (P < 0.005) and an 87% increase in GSH-GSSG efflux (P < 0.005). This increased oxidation of GSH indicates that toxicity of NF is likely oxidative in nature, possibly via redox cycling of NF in the presence of O2 to generate activated oxygen species. Activities of glucose-6-phosphate and 6-phosphogluconate dehydrogenases, GSH reductase and GSH S-transferase were not significantly different due to NF perfusion. GSH peroxidase activity decreased 34% (P < 0.025) in NF-perfused lungs. Because all TLG, as well as total nonprotein thiol was accounted for in NF-perfused lungs, it would appear that no GSH-NF metabolite conjugation occurred. GSH metabolic conjugation in the perfused lung is easily detected when tissue-alkylating drugs on their metabolites are present.