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Increased glomerular and urinary malondialdehyde in puromycin aminonucleoside-induced proteinuria in rats
R N Srivastava1, S Diven, A Kalia
1Department of Pediatrics, University of Texas Medical Branch, Galveston 77555, USA.
Abstract:
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.
Insights
Puromycin aminonucleoside (PAN) causes kidney damage through reactive oxygen metabolites (ROM). Increased urinary malondialdehyde (MDA) indicates lipid peroxidation and serves as a marker for this PAN-induced glomerular injury.
Area of Science:
- Nephrology
- Biochemistry
- Toxicology
Background:
- Puromycin aminonucleoside (PAN) induces proteinuria in rats, potentially via reactive oxygen metabolites (ROM).
- Lipid peroxidation, indicated by malondialdehyde (MDA) production, is a key cellular injury mechanism.
- Understanding the role of ROM in PAN nephrotoxicity is crucial for developing protective strategies.
Purpose of the Study:
- To investigate if PAN administration increases glomerular MDA content and urinary MDA excretion in rats.
- To determine if dimethylthiourea (DMTU), a free radical scavenger, can mitigate PAN-induced increases in MDA and protect against glomerular injury.
- To establish urinary MDA excretion as a potential biomarker for ROM-mediated lipid peroxidation in PAN nephrotoxicity.
Main Methods:
- Three groups of Sprague-Dawley rats were used: control, PAN-treated, and PAN + DMTU-treated.
- Proteinuria and urinary MDA levels were monitored over time post-PAN administration.
- Glomerular MDA content was measured at sacrifice (day 8) to assess lipid peroxidation.
- DMTU was administered to assess its protective effects against PAN toxicity.
Main Results:
- PAN-induced proteinuria developed in rats, starting on day 4.
- Glomerular MDA content was significantly elevated in PAN-treated rats compared to controls.
- Urinary MDA levels markedly increased in PAN-treated rats from day 3 onwards.
- DMTU treatment protected against PAN-induced increases in glomerular MDA and urinary MDA excretion, and prevented proteinuria.
Conclusions:
- Reactive oxygen metabolites (ROM) are implicated in PAN-induced glomerular injury.
- Increased urinary MDA excretion serves as a reliable marker for ROM-mediated lipid peroxidation in PAN nephrotoxicity.
- DMTU demonstrates a protective effect against PAN-induced kidney damage, supporting the role of free radicals.