Abstract
Nitrofurantoin, a commonly used urinary antiseptic, is associated with significant pulmonary toxicity. This study used a 51Cr rat lung explant cytotoxicity assay to demonstrate that nitrofurantoin (10-3 M), when incubated with lung parenchymal cells for 12 h at 37° C, resulted in significant lung cell injury (cytotoxic index of 43 ± 2). This injury could be reduced (p < 0.05) by several antioxidants, including superoxide dismutase, 300 U/ml (37 ± 2); catatase, 1,100 U/ml (27 ± 2); αtocopherol, 10 μg/ml(30 ± 2); ascorbic acid 50 μglml (37 ± 2); ethanol, 0.1% (35 ± 2); dimethyl sulfoxide, 1.0% (37 ± 2). Additionally, the nitrofurantoin-induced injury could be accelerated in the presence of hyperoxia (95% O2) from 45 ± 2 to 62 ± 1, p < 0.01. These data suggest that nitrofurantoin can directly injure lung parenchymal cells, probably through oxidant mechanisms, and this might suggest alternative approaches in the evaluation and therapy of patients with this disorder.