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

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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.

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Acknowledgments

This study was supported by Hungarian National Scientific Research Grant OTKA K67895 and by a Research & Development Grant of the Hungarian Society of Nephrology. T. Csont holds a János Bolyai Research Fellowship of the Hungarian Academy of Sciences.

Conflict of interest

The authors have declared that no conflict of interest exists.

Author information

Authors and Affiliations

  1. Department of Pediatrics, Albert Szent-Györgyi Clinical Center, University of Szeged, Korányi fasor 14-15, Szeged, 6720, Hungary

    Péter Monostori, Zsuzsanna Ökrös, Orsolya Czétényi, Zoltán Kiss, Balázs Gellén, Csaba Bereczki & Sándor Túri

  2. Cardiovascular Research Group, Department of Biochemistry, University of Szeged, Dóm tér 9, Szeged, 6720, Hungary

    Gabriella F. Kocsis, Péter Bencsik, Imre Ocsovszki, Judit Pipis, János Pálóczi, Márta Sárközy, Szilvia Török, Tamás Csont & Péter Ferdinandy

  3. Pharma Hungary Group, Dóm tér 9, Szeged, Szeged, 6720, Hungary

    Gabriella F. Kocsis, Péter Bencsik, Judit Pipis, Márta Sárközy, Eszter Fodor, Tamás Csont & Péter Ferdinandy

  4. Department of Biochemistry and Molecular Biology, University of Szeged, Közép fasor 52, Szeged, 6726, Hungary

    Ilona S. Varga

  5. Department of Nephrology-Hypertension, St Imre Teaching Hospital, Tétényi út 12-16, Budapest, 1115, Hungary

    István Kiss

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  1. Péter Monostori
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  2. Gabriella F. Kocsis
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  15. István Kiss
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  17. Tamás Csont
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Correspondence to Péter Monostori.

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Monostori, P., Kocsis, G.F., Ökrös, Z. et al. Different administration schedules of darbepoetin alfa affect oxidized and reduced glutathione levels to a similar extent in 5/6 nephrectomized rats. Clin Exp Nephrol 17, 569–574 (2013). https://doi.org/10.1007/s10157-012-0749-5

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  • DOI: https://doi.org/10.1007/s10157-012-0749-5

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