Protective effect of erythropoietin against radiocontrast-induced renal tubular epithelial cell injury

Am J Nephrol. 2008;28(2):203-9. doi: 10.1159/000110089. Epub 2007 Oct 24.

Abstract

Background/aims: Recombinant human erythropoietin (rhEpo) has been shown to reduce tissue injury following ischemia-reperfusion. We examined whether rhEpo protects in vitro renal tubular epithelial cells against radiocontrast media-induced injury.

Methods: LLC-PK1 renal tubular epithelial cells were exposed to non-ionic radiocontrast agent iohexol (low-osmolar) or iodixanol (iso-osmolar), with or without rhEpo (200 U/ml). Following a 6-hour exposure, cells were incubated for 24 h in radiocontrast-free culture medium. Cell viability was then assessed by the MTT assay. We also assessed cell apoptosis by the TUNEL assay, and activities of caspase-3, caspase-8, and caspase-9 were determined by a luminescence assay.

Results: rhEpo improved viability of iohexol-treated LLC-PK1 cells by 27 +/- 6% (88.1 +/- 1.5 vs. 70.8 +/- 3.3%, p = 0.008). Similarly, rhEpo improved the viability of iodixanol-treated LLC-PK1 cells by 26 +/- 4% (82.5 +/- 2.1vs. 65.7 +/- 1.7%, p = 0.028). rhEpo also decreased apoptosis rates of iohexol-treated LLC-PK1 cells (6.4 +/- 0.9/1,000 cells vs. 14.8 +/- 2.4/1,000 cells, p = 0.028), and iodixanol-treated LLC-PK1 cells (8.0 +/- 1.2/1,000 cells vs. 13.5 +/- 1.9/1,000 cells, p = 0.028). In iohexol-treated LLC-PK1 cells, rhEpo attenuated activation of caspase-3 (p = 0.003), caspase-8 (p = 0.033) and caspase-9 (p = 0.055).

Conclusion: rhEpo attenuates in vitro renal tubular epithelial cell injury induced by low- and iso-osmolar radiocontrast media, possibly by reduction of caspases activation and apoptosis rates.

MeSH terms

  • Animals
  • Apoptosis
  • Caspases / metabolism
  • Cell Survival
  • Contrast Media / adverse effects*
  • Contrast Media / pharmacology
  • Enzyme Activation
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology*
  • Erythropoietin / therapeutic use*
  • In Situ Nick-End Labeling
  • Iohexol / pharmacology
  • Kidney Tubules / cytology*
  • Kidney Tubules / metabolism
  • LLC-PK1 Cells
  • Recombinant Proteins
  • Reperfusion Injury
  • Swine
  • Triiodobenzoic Acids / pharmacology

Substances

  • Contrast Media
  • Recombinant Proteins
  • Triiodobenzoic Acids
  • Erythropoietin
  • Iohexol
  • Caspases
  • iodixanol