A single
intravenous injection of
puromycin aminonucleoside (PAN) results in marked
proteinuria and glomerular morphological changes that are similar to
minimal change disease in humans. We examined the effect of
hydroxyl radical scavengers and an
iron chelator on PAN-induced
proteinuria. PAN in a dose of 5 mg/100 g body wt significantly increased urinary
protein by day 5 (saline: 15 +/- 2, N = 24: PAN: 63 +/- 17, N = 23, P less than 0.001); the
proteinuria rapidly increased thereafter, reaching 216 +/- 34, N = 23 by day 7. Concurrent administration of
hydroxyl radical scavengers
dimethylthiourea, (
DMTU 500 mg/kg followed by 125 mg/kg i.p. twice a day) and
sodium benzoate (BENZ, 150 mg/kg followed by 125 mg/kg i.p. twice a day) starting the evening before PAN injection markedly reduced
proteinuria throughout the course of the study (urinary
protein, mg/24 hours on day 7, mean +/- SEM: PAN: 229 +/- 45, N = 15; PAN +
DMTU: 30 +/- 5, N = 18; PAN + BENZ: 80 +/- 18, N = 16. Because of the participation of
iron in
biological systems to generate
hydroxyl radical, we also examined the effect of
deferoxamine (DFO, 30 mg/day), an
iron chelator, on the PAN-induced
proteinuria. Concurrent administration of DFO was also protective. In a second series of experiments,
DMTU and DFO (administered as described above and then for two additional days after the PAN) provided marked protection even when they were stopped prior to the onset of
proteinuria. The protective effects of two
hydroxyl radical scavengers and
iron chelator implicate an important role for
hydroxyl radical in PAN-induced
nephrotic syndrome.