Clinical and Experimental Nephrology

, Volume 17, Issue 4, pp 569–574

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

  • Péter Monostori
  • Gabriella F. Kocsis
  • Zsuzsanna Ökrös
  • Péter Bencsik
  • Orsolya Czétényi
  • Zoltán Kiss
  • Balázs Gellén
  • Csaba Bereczki
  • Imre Ocsovszki
  • Judit Pipis
  • János Pálóczi
  • Márta Sárközy
  • Szilvia Török
  • Ilona S. Varga
  • István Kiss
  • Eszter Fodor
  • Tamás Csont
  • Péter Ferdinandy
  • Sándor Túri
Original Article

Abstract

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.

Keywords

Chronic kidney disease Erythropoiesis-stimulating agent (ESA) Erythropoietin Glutathione Oxidative stress Subtotal nephrectomy 

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Copyright information

© Japanese Society of Nephrology 2012

Authors and Affiliations

  • Péter Monostori
    • 1
  • Gabriella F. Kocsis
    • 2
    • 3
  • Zsuzsanna Ökrös
    • 1
  • Péter Bencsik
    • 2
    • 3
  • Orsolya Czétényi
    • 1
  • Zoltán Kiss
    • 1
  • Balázs Gellén
    • 1
  • Csaba Bereczki
    • 1
  • Imre Ocsovszki
    • 2
  • Judit Pipis
    • 2
    • 3
  • János Pálóczi
    • 2
  • Márta Sárközy
    • 2
    • 3
  • Szilvia Török
    • 2
  • Ilona S. Varga
    • 4
  • István Kiss
    • 5
  • Eszter Fodor
    • 3
  • Tamás Csont
    • 2
    • 3
  • Péter Ferdinandy
    • 2
    • 3
  • Sándor Túri
    • 1
  1. 1.Department of Pediatrics, Albert Szent-Györgyi Clinical CenterUniversity of SzegedSzegedHungary
  2. 2.Cardiovascular Research Group, Department of BiochemistryUniversity of SzegedSzegedHungary
  3. 3.Pharma Hungary GroupSzegedHungary
  4. 4.Department of Biochemistry and Molecular BiologyUniversity of SzegedSzegedHungary
  5. 5.Department of Nephrology-HypertensionSt Imre Teaching HospitalBudapestHungary

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