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, C. Bereczki, I. Ocsovszki, Judit Pipis, János Pálóczi, Márta Sárközy, Szilvia Török, I. Varga, István Kiss, Eszter Fodor, T. Csont, P. Ferdinándy, S. Túri

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)569-574
Number of pages6
JournalClinical and Experimental Nephrology
Volume17
Issue number4
DOIs
Publication statusPublished - Aug 2013

Fingerprint

Glutathione Disulfide
Hematinics
Glutathione
Appointments and Schedules
Oxidative Stress
Chronic Renal Insufficiency
Hemoglobins
Darbepoetin alfa
Serum
salicylhydroxamic acid
Therapeutics

Keywords

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

ASJC Scopus subject areas

  • Nephrology
  • Physiology
  • Physiology (medical)

Cite this

Different administration schedules of darbepoetin alfa affect oxidized and reduced glutathione levels to a similar extent in 5/6 nephrectomized rats. / Monostori, Péter; Kocsis, Gabriella F.; Ökrös, Zsuzsanna; Bencsik, Péter; Czétényi, Orsolya; Kiss, Zoltán; Gellén, Balázs; Bereczki, C.; Ocsovszki, I.; Pipis, Judit; Pálóczi, János; Sárközy, Márta; Török, Szilvia; Varga, I.; Kiss, István; Fodor, Eszter; Csont, T.; Ferdinándy, P.; Túri, S.

In: Clinical and Experimental Nephrology, Vol. 17, No. 4, 08.2013, p. 569-574.

Research output: Contribution to journalArticle

Monostori, Péter ; Kocsis, Gabriella F. ; Ökrös, Zsuzsanna ; Bencsik, Péter ; Czétényi, Orsolya ; Kiss, Zoltán ; Gellén, Balázs ; Bereczki, C. ; Ocsovszki, I. ; Pipis, Judit ; Pálóczi, János ; Sárközy, Márta ; Török, Szilvia ; Varga, I. ; Kiss, István ; Fodor, Eszter ; Csont, T. ; Ferdinándy, P. ; Túri, S. / Different administration schedules of darbepoetin alfa affect oxidized and reduced glutathione levels to a similar extent in 5/6 nephrectomized rats. In: Clinical and Experimental Nephrology. 2013 ; Vol. 17, No. 4. pp. 569-574.
@article{ea38c181d9454ca9ab989c52d28a7ece,
title = "Different administration schedules of darbepoetin alfa affect oxidized and reduced glutathione levels to a similar extent in 5/6 nephrectomized rats",
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",
author = "P{\'e}ter Monostori and Kocsis, {Gabriella F.} and Zsuzsanna {\"O}kr{\"o}s and P{\'e}ter Bencsik and Orsolya Cz{\'e}t{\'e}nyi and Zolt{\'a}n Kiss and Bal{\'a}zs Gell{\'e}n and C. Bereczki and I. Ocsovszki and Judit Pipis and J{\'a}nos P{\'a}l{\'o}czi and M{\'a}rta S{\'a}rk{\"o}zy and Szilvia T{\"o}r{\"o}k and I. Varga and Istv{\'a}n Kiss and Eszter Fodor and T. Csont and P. Ferdin{\'a}ndy and S. T{\'u}ri",
year = "2013",
month = "8",
doi = "10.1007/s10157-012-0749-5",
language = "English",
volume = "17",
pages = "569--574",
journal = "Clinical and Experimental Nephrology",
issn = "1342-1751",
publisher = "Springer Japan",
number = "4",

}

TY - JOUR

T1 - Different administration schedules of darbepoetin alfa affect oxidized and reduced glutathione levels to a similar extent in 5/6 nephrectomized rats

AU - Monostori, Péter

AU - Kocsis, Gabriella F.

AU - Ökrös, Zsuzsanna

AU - Bencsik, Péter

AU - Czétényi, Orsolya

AU - Kiss, Zoltán

AU - Gellén, Balázs

AU - Bereczki, C.

AU - Ocsovszki, I.

AU - Pipis, Judit

AU - Pálóczi, János

AU - Sárközy, Márta

AU - Török, Szilvia

AU - Varga, I.

AU - Kiss, István

AU - Fodor, Eszter

AU - Csont, T.

AU - Ferdinándy, P.

AU - Túri, S.

PY - 2013/8

Y1 - 2013/8

N2 - 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.

AB - 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.

KW - Chronic kidney disease

KW - Erythropoiesis-stimulating agent (ESA)

KW - Erythropoietin

KW - Glutathione

KW - Oxidative stress

KW - Subtotal nephrectomy

UR - http://www.scopus.com/inward/record.url?scp=84883287152&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84883287152&partnerID=8YFLogxK

U2 - 10.1007/s10157-012-0749-5

DO - 10.1007/s10157-012-0749-5

M3 - Article

VL - 17

SP - 569

EP - 574

JO - Clinical and Experimental Nephrology

JF - Clinical and Experimental Nephrology

SN - 1342-1751

IS - 4

ER -