Impact of short-duration administration of N-acetylcysteine, probucol and ascorbic acid on contrast-induced cytotoxicity

J Nephrol. 2012 Jan-Feb;25(1):56-62. doi: 10.5301/JN.2011.7741.

Abstract

Background: The best pharmaceutical prevention of contrast-medium-induced nephropathy for emergency procedures remains unknown. The aim of this study was to examine the impact of short-duration antioxidant pretreatment on contrast-medium-induced cytotoxicity.

Methods: Human embryonic kidney cells were treated with three different contrast media: ionic ioxitalamate, non-ionic low-osmolar iopromide, and iso-osmolar iodixanol. The doses and durations of pretreatment with antioxidants were 2 mM/L N-acetylcysteine for 15 minutes, 40 µM/L probucol for 30 minutes, and 30 µM/L ascorbic acid for 30 minutes. A supplementary dose of 2 mM/L N-acetylcysteine was administered 12 hours after contrast medium treatment. Cell viability was determined by tetrazolium MTT assay.

Results: All three contrast media caused significant reduction of cell viability at 24 hours (p<0.001). In the groups receiving iopromide or iodixanol, N-acetylcysteine pretreatment significantly improved cell viability compared with no N-acetylcysteine pretreatment (p<0.001). In the group receiving ioxitalamate, N-acetylcysteine pretreatment followed by a supplementary dose of N-acetylcysteine at 12 hours rather than N-acetylcysteine pretreatment alone significantly improved cell viability compared with no N-acetylcysteine pretreatment (p=0.038). Probucol or ascorbic acid pretreatment was unable to reduce cell death caused by the three contrast media.

Conclusions: Short-duration pretreatment with N-acetylcysteine significantly reduced contrast-medium-induced cytotoxicity. These findings provide new insight into the prevention of contrast-medium-induced nephropathy in clinical emergency scenarios.

MeSH terms

  • Acetylcysteine / pharmacology
  • Analysis of Variance
  • Antioxidants / pharmacology*
  • Apoptosis / drug effects
  • Ascorbic Acid / pharmacology
  • Cell Survival / drug effects*
  • Cells, Cultured
  • Contrast Media / adverse effects*
  • Free Radical Scavengers / pharmacology*
  • Humans
  • Iohexol / adverse effects
  • Iohexol / analogs & derivatives
  • Iothalamic Acid / adverse effects
  • Iothalamic Acid / analogs & derivatives
  • Kidney / cytology
  • Kidney / drug effects*
  • Probucol / pharmacology
  • Time Factors
  • Triiodobenzoic Acids / adverse effects

Substances

  • Antioxidants
  • Contrast Media
  • Free Radical Scavengers
  • Triiodobenzoic Acids
  • Iothalamic Acid
  • Iohexol
  • iopromide
  • ioxitalamic acid
  • iodixanol
  • Probucol
  • Ascorbic Acid
  • Acetylcysteine