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

Abstract

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. 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. 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. 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.