Evidence suggesting a role for hydroxyl radical in puromycin aminonucleoside-induced proteinuria

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