Nitrofurantoin-induced pulmonary toxicity. In vivo evidence for oxidative stress-mediated mechanisms.
The present study was carried out to examine whether nitrofurantoin-induced pulmonary toxicity in normal rats was mediated via oxidant stress mechanisms. The relative importance of the cellular antioxidant enzymes in nitrofurantoin toxicity was also assessed. For this, the pulmonary toxicity induced by nitrofurantoin in rats was evaluated at various time intervals after a single subcutaneous injection. Data from this study showed that nitrofurantoin (200 mg/kg, s.c.) resulted in transient but measurable lung damage as evidenced by the increases in wet lung weight/body weight ratio and decreases in lung angiotensin converting enzyme activity. A transient decrease in GSH concentrations with a concurrent increase in GSSG concentrations as well as an increase in lipid peroxidation levels (measured by the formation of diene conjugates and thiobarbituric acid reactants) were also evident in lungs of nitrofurantoin-treated rats. In addition, nitrofurantoin did not alter the pulmonary superoxide dismutase and glutathione peroxidase activities, but it did produce transient decreases in catalase and glutathione reductase activities. These data indicate that impairment of the ability of the lung to detoxify reactive oxygen species may play an important role in the development of nitrofurantoin-induced pulmonary toxicity. The results of the present study suggest that nitrofurantoin can damage the lungs of rats, probably through oxidative stress-mediated mechanisms. Also, our data have provided in vivo evidence for substantiating lipid peroxidation as a possible cause of lung damage.
Suntres
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ZE
Biosciences Division, Defence and Civil Institute of Environmental Medicine, North York, Ontario, Canada.
Shek
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PN
D000818:Animals; D001835:Body Weight; D002374:Catalase / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D007279:Injections, Subcutaneous; D015227:Lipid Peroxidation / Q000187:drug effects; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008956:Models, Chemical; D009582:Nitrofurantoin / Q000008:administration & dosage / Q000633:toxicity*; D009929:Organ Size; D010084:Oxidation-Reduction; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000378:metabolism; D013858:Thiobarbiturates
D013858:Thiobarbiturates; D009582:Nitrofurantoin; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D007703:Peptidyl-Dipeptidase A; C029684:thiobarbituric acid