N-acetylcysteine protects rats with chronic renal failure from gadolinium-chelate nephrotoxicity

PLoS One. 2012;7(7):e39528. doi: 10.1371/journal.pone.0039528. Epub 2012 Jul 16.

Abstract

The aim of this study was to evaluate the effect of Gd-chelate on renal function, iron parameters and oxidative stress in rats with CRF and a possible protective effect of the antioxidant N-Acetylcysteine (NAC). Male Wistar rats were submitted to 5/6 nephrectomy (Nx) to induced CRF. An ionic-cyclic Gd (Gadoterate Meglumine) was administrated (1.5 mM/KgBW, intravenously) 21 days after Nx. Clearance studies were performed in 4 groups of anesthetized animals 48 hours following Gd- chelate administration: 1--Nx (n = 7); 2--Nx+NAC (n = 6); 3--Nx+Gd (n = 7); 4--Nx+NAC+Gd (4.8 g/L in drinking water), initiated 2 days before Gd-chelate administration and maintained during 4 days (n = 6). This group was compared with a control. We measured glomerular filtration rate, GFR (inulin clearance, ml/min/kg BW), proteinuria (mg/24 hs), serum iron (µg/dL); serum ferritin (ng/mL); transferrin saturation (%), TIBC (µg/dL) and TBARS (nmles/ml). Normal rats treated with the same dose of Gd-chelate presented similar GFR and proteinuria when compared with normal controls, indicating that at this dose Gd-chelate is not nephrotoxic to normal rats. Gd-chelate administration to Nx-rats results in a decrease of GFR and increased proteinuria associated with a decrease in TIBC, elevation of ferritin serum levels, transferrin oversaturation and plasmatic TBARS compared with Nx-rats. The prophylactic treatment with NAC reversed the decrease in GFR and the increase in proteinuria and all alterations in iron parameters and TBARS induced by Gd-chelate. NAC administration to Nx rat did not modify the inulin clearance and iron kinetics, indicating that the ameliorating effect of NAC was specific to Gd-chelate. These results suggest that NAC can prevent Gd-chelate nephrotoxicity in patients with chronic renal failure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / pharmacology*
  • Animals
  • Chelating Agents / chemistry
  • Chelating Agents / toxicity*
  • Gadolinium / chemistry*
  • Glomerular Filtration Rate
  • Inulin / pharmacokinetics
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / physiopathology
  • Kidney Failure, Chronic / metabolism*
  • Kidney Failure, Chronic / physiopathology*
  • Male
  • Rats
  • Rats, Wistar
  • Thiobarbituric Acid Reactive Substances / metabolism

Substances

  • Chelating Agents
  • Thiobarbituric Acid Reactive Substances
  • Inulin
  • Gadolinium
  • Acetylcysteine