Crypto - OH^. radical production by nitrofurantoin

The well-known bactericidal agent, nitrofurantoin (NF), has been in widespread use for more than a quarter of a century, mainly for the treatment of acute infections of the urinary tract (1 - 3). However, pulmonary fibrosis frequently occurs on prolonged treatment with the drug, which bears a resemblance to paraquat (MV) induced damage. Previous studies have indicated that NF might be able to reductively activate oxygen (4,5) in a similar manner to MV (6). Recently, we have provided evidence for the generation of a strong oxidising species, the crypto-OH^. radical, from an electron donor and H₂O₂ (7,8). In the present communication, we describe the results of an investigation to discover whether NF was able to generate this potentially damaging species. Earlier work on the reduction of NF was performed using microsomal fractions or partially purified enzyme. The studies reported here were conducted with pure preparations of NADPH - cytochrome c reductase and xanthine oxidase.