Preclinical evaluation of erythropoietin administration in a model of radiation-induced kidney dysfunction

Int J Radiat Oncol Biol Phys. 2006 Apr 1;64(5):1513-8. doi: 10.1016/j.ijrobp.2005.11.042.

Abstract

Purpose: To test whether the clinically available growth factor erythropoietin (EPO) influences radiation-induced normal-tissue damage in a model of kidney dysfunction.

Methods: Animal experiments were conducted to test the role of EPO administration in a C3H mouse model of unilateral kidney irradiation with 6, 8, and 10 Gy and to assess the effects of 2 different dose levels of EPO. The kidney function was assessed before radiotherapy, as well as 19, 25, 31, and 37 weeks thereafter by means of (99m)Tc-dimercaptosuccinat scans (static scintigraphy).

Results: Concomitant EPO administration significantly increased the degree of radiation-induced kidney dysfunction. A dose of 2,000 IU/kg body weight per injection tended to cause more damage than the lower dose of 500 IU/kg.

Conclusion: Administration of growth factors concomitant to radiotherapy might modify the development of kidney dysfunction. Although insulin-like growth factor-1 has previously been shown to protect the kidney, such an effect could not be demonstrated for EPO. The latter agent even increased the development of nephropathy.

MeSH terms

  • Animals
  • Dose-Response Relationship, Radiation
  • Epoetin Alfa
  • Erythropoietin / administration & dosage
  • Erythropoietin / adverse effects*
  • Female
  • Glomerular Filtration Rate
  • Kidney / diagnostic imaging
  • Kidney / drug effects
  • Kidney / radiation effects*
  • Mice
  • Mice, Inbred C3H
  • Radiation Injuries, Experimental / diagnostic imaging
  • Radiation Injuries, Experimental / physiopathology
  • Radiation Injuries, Experimental / prevention & control*
  • Radiation Tolerance / drug effects*
  • Radiation Tolerance / physiology
  • Radionuclide Imaging
  • Radiopharmaceuticals
  • Recombinant Proteins
  • Technetium Tc 99m Dimercaptosuccinic Acid
  • Time Factors

Substances

  • Radiopharmaceuticals
  • Recombinant Proteins
  • Erythropoietin
  • Technetium Tc 99m Dimercaptosuccinic Acid
  • Epoetin Alfa