N-Acetylcysteine Ameliorates Amphotericin-Induced Nephropathy in Rats

Abstract

Background: Amphotericin B may cause acute reduction in renal function. N-acetylcysteine (NAC) has a renoprotective activity in several nephrotoxic renal insults, but its effect on amphotericin-induced renal failure has not been investigated yet. Methods: Acute renal failure was induced in 30 Sprague-Dawley rats by a single intraperitoneal injection of amphotericin B (50 mg/kg). NAC (10 mg/kg) in isotonic saline or isotonic saline alone were administered daily for 4 days, starting 1 day before the amphotericin B injection. Glomerular filtration rate (GFR) was assessed using 99m-technetium diethylene triaminepentaacetic acid. Before and following amphotericin B administration, a 24-hour urine collection was performed for sodium, potassium and magnesium determination. The kidneys were preserved for pathologic examination. Results: Amphotericin B induced a significant decrease of GFR in both groups. Four days after amphotericin injection the GFR in the NAC-treated group was significantly higher than in the control group (0.62 ± 0.20 vs. 0.46 ± 0.14 ml/min, p = 0.042). Histologic signs of acute tubular necrosis were attenuated in the NAC-treated group. There were no significant differences between the groups in sodium, potassium and magnesium urine excretion after amphotericin injection. Conclusions: NAC treatment exerted a renoprotective effect on deterioration of GFR in a rat model of amphotericin-induced renal failure. No functional protection on tubular function, as obviated by similar polyuria and urine losses of potassium and magnesium in both groups, was observed.

Reduction of Amphotericin B-Induced Renal Tubular Apoptosis by N -Acetylcysteine

“…Nitescu et al showed that treatment with 200 mg/kg NAC decreases the GFR and reduces plasma creatinine levels, hyperkalemia, and systemic oxidative stress in rats subjected to renal ischemic injury (20). In another study, prophylactic NAC prevented decreases in the GFR associated with high doses of AmB (12). Although we could show that NAC significantly reduced the AmB-induced tubular apoptosis, we did not evaluate the electrolytes in serum or urine samples or the serum creatinine levels because of technical unavailability.…”

“…with two doses of 30, 60, and 120 mg of NAC/kg/day, respectively, for five consecutive days. The doses of AmB (32) and NAC (1,12) were determined based on data from the literature. Another five animals (group E) were treated with sterile water only.…”

Differential Effects of N-Acetylcysteine, Theophylline or Bicarbonate on Contrast-Induced Rat Renal Vasoconstriction

“…It seems therefore of great importance that injection of NAC prior to CM administration resulted in an immediate, profound amplification of PGE 2 synthesis that sustained for at least half an hour. Thus far, beneficial effects of NAC treatment have been observed in a number of toxic and ischemic injury models [12,17,18,19,20,21], including CIN [18, 22]. The effects proved to be cell/organ-specific, so it is not surprising that the underlying mechanisms are diverse.…”

A double-blinded, placebo-controlled, multicenter clinical trial ofN-acetylcysteine for preventing amphotericin B-induced nephrotoxicity

“…NAC administration as a preventive measure for patients at high risk of contrast-induced nephropathy has been suggested by the 2012 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines (2D) [10]. Furthermore, two published experimental studies in rat models implicated that AmBinduced GFR reduction, renal tubular apoptosis and histological signs of acute tubular necrosis (ATN) can be ameliorated by the intraperitoneal co-administration of NAC [11,12].…”