Efficacy of the combination of N-acetylcysteine and desferrioxamine in the prevention and treatment of gentamicin-induced acute renal failure in male Wistar rats

Background. Oxidative stress and the formation of aminoglycoside–iron complexes through iron-dependent Fenton reaction have been proposed to be the major mechanisms in the development of GM-induced acute renal failure (ARF); however, the efficacy of the combination of N-acetylcysteine (NAC) and desf...

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Published in:Nephrology, dialysis, transplantation dialysis, transplantation, 2009-07, Vol.24 (7), p.2077-2082
Main Authors: Petronilho, Fabricia, Constantino, Larissa, de Souza, Bruna, Reinke, Adalisa, Martins, Márcio Rodrigo, Fraga, Cassiana Mazon, Ritter, Cristiane, Dal-Pizzol, Felipe
Format: Article
Language:English
Subjects:
Acetylcysteine - administration & dosage
Acute Kidney Injury - chemically induced
Acute Kidney Injury - drug therapy
Acute Kidney Injury - prevention & control
acute renal failure
Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
Animals
Biological and medical sciences
Deferoxamine - administration & dosage
desferrioxamine
Drug Therapy, Combination
Emergency and intensive care: renal failure. Dialysis management
Free Radical Scavengers - administration & dosage
gentamicin
Gentamicins - administration & dosage
Intensive care medicine
Male
Medical sciences
N-acetylcysteine
Nephrology. Urinary tract diseases
Nephropathies. Renovascular diseases. Renal failure
oxidative stress
Rats
Rats, Wistar
Renal failure
Siderophores - administration & dosage
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Summary:Background. Oxidative stress and the formation of aminoglycoside–iron complexes through iron-dependent Fenton reaction have been proposed to be the major mechanisms in the development of GM-induced acute renal failure (ARF); however, the efficacy of the combination of N-acetylcysteine (NAC) and desferrioxamine (DFX) in the prevention and the treatment of GM-induced ARF has not previously been investigated. Methods. In the prevention protocol, adult male Wistar rats received gentamicin (GM) [70 mg/kg, intraperitoneally (i.p), each 12 h for 7 days], NAC (20 mg/kg, sc, each 8 h for 7 days) and/or DFX (20 mg/kg, sc, at first, fourth and seventh days). In the treatment protocol animals received GM for 7 days. Additionally, animals received NAC and or DFX starting in the fourth day after GM administration. Parameters of renal function had been evaluated 24 h, 4 and 8 days after the beginning of GM administration in the prevention protocol and in Days 5 and 8 in the treatment protocol. At the end of experiment, lipid peroxidation (TBARS assay) and protein oxidation (protein carbonyls levels) formation were evaluated in kidney tissue as oxidative damage parameters. Results. In the prevention protocol, GM-induced ARF was prevented by the NAC and DFX association. Lipid peroxidation was attenuated by both antioxidant treatments, but the effects of NAC plus DFX were of greater magnitude. In the treatment protocol, plasma markers of renal injury were improved only in the NAC group, despite the similar antioxidant effect of both NAC, DFX and NAC plus DFX. Conclusion. Although the combination of NAC and DFX was more effective in the prevention protocol, the use of NAC alone seemed to be superior to NAC–DFX combination, in the treatment of GM-induced ARF in adult male Wistar rats.
ISSN:0931-0509
1460-2385
DOI:10.1093/ndt/gfn774