Increased glomerular and urinary malondialdehyde in puromycin aminonucleoside-induced proteinuria in rats.
Puromycin aminonucleoside (PAN)-induced proteinuria in rats may be mediated by reactive oxygen metabolites (ROM), which are injurious to several cell components including membrane lipids. Increased malondialdehyde (MDA) production is indicative of lipid peroxidation. We examined if MDA content of glomeruli and its urinary excretion were increased in rats administered PAN. Of three groups of 8 Sprague-Dawley rats each, group 1 served a control, group 2 animals received a single intravenous injection of PAN (5 mg/100 g body weight) and group 3 animals PAN with intraperitoneal injections of dimethylthiourea (DMTU), a free radical scavenger of oxidants such as hydroxyl radicals, for 4 days. The rats were sacrificed on day 8 after PAN injection. Increasing proteinuria, starting on day 4, developed in animals in group 2 but not in the others. The glomerular MDA (nmol/mg protein) in group 2 animals was 2.93 +/- 1.91, significantly higher than 0.87 +/- 0.63 and 1.26 +/- 0.76 in groups 1 and 3, respectively. Urinary levels of MDA markedly increased in group 2 rats on day 3 and remained high thereafter, but no such increase occurred in the control animals and those administered PAN with DMTU; the latter was thus protective against PAN toxicity. Our observations support the view that ROM are involved in PAN-induced glomerular injury and that increased urinary MDA excretion can be a marker of ROM-mediated lipid peroxidation.
Srivastava
R N
RN
Department of Pediatrics, University of Texas Medical Branch, Galveston 77555, USA.
Diven
S
S
Kalia
A
A
Travis
L B
LB
Ansari
N H
NH
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D016166:Free Radical Scavengers; D007678:Kidney Glomerulus / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000502:physiology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism* / Q000652:urine; D011507:Proteinuria / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control; D011692:Puromycin Aminonucleoside; D051381:Rats; D017207:Rats, Sprague-Dawley; D013890:Thiourea / Q000031:analogs & derivatives / Q000627:therapeutic use
D001798:Blood Proteins; D016166:Free Radical Scavengers; D008315:Malondialdehyde; D011692:Puromycin Aminonucleoside; C038983:1,3-dimethylthiourea; D013890:Thiourea