Different administration schedules of darbepoetin alfa affect oxidized and reduced glutathione levels to a similar extent in 5/6 nephrectomized rats

Clin Exp Nephrol. 2013 Aug;17(4):569-74. doi: 10.1007/s10157-012-0749-5. Epub 2012 Dec 6.


Background: The development of erythropoiesis-stimulating agents (ESAs) with extended serum half-lives has allowed marked prolongation of the administration intervals. The level of oxidative stress is increased in chronic kidney disease, and is reportedly decreased after long-term ESA treatment. However, the effect of different dosing regimens of ESAs on oxidative stress has not been elucidated.

Methods: Five-sixths nephrectomized (NX) rats received either 0.4 μg/kg darbepoetin alfa (DA) weekly or 0.8 μg/kg DA fortnightly between weeks 4 and 10. NX animals receiving saline and a sham-operated (SHAM) group served as controls. The levels of oxidized and reduced glutathione (GSSG, GSH) were followed from blood samples drawn fortnightly.

Results: During the follow-up, the ratios GSSG/GSH showed similar trends in both DA groups, levels being significantly lower than those in the SHAM group at weeks 8 and 10. GSSG levels were lower than the baseline throughout the study in all groups except for NX controls. The GSH levels were increased in all three NX groups (weeks 6-10) compared with both the baseline and the SHAM group

Conclusion: Our results suggest that the extent of oxidative stress is similar in response to different dosing regimens of DA in 5/6 NX rats when comparable hemoglobin levels are maintained. These findings remain to be confirmed in chronic kidney disease patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Darbepoetin alfa
  • Drug Administration Schedule
  • Erythropoietin / administration & dosage
  • Erythropoietin / analogs & derivatives*
  • Glutathione / blood*
  • Glutathione Disulfide / blood*
  • Hematinics / administration & dosage*
  • Male
  • Nephrectomy
  • Oxidative Stress
  • Rats


  • Hematinics
  • Erythropoietin
  • Darbepoetin alfa
  • Glutathione
  • Glutathione Disulfide