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
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pediatrics, Albert Szent-Györgyi Clinical Center, University of Szeged, Korányi fasor 14-15, Szeged, 6720, Hungary. monostoripeter@gmail.com
authors.forename: Péter
authors.initials: P
authors.lastname: Monostori
authors.forename: Gabriella F
authors.initials: GF
authors.lastname: Kocsis
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Ökrös
authors.forename: Péter
authors.initials: P
authors.lastname: Bencsik
authors.forename: Orsolya
authors.initials: O
authors.lastname: Czétényi
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Kiss
authors.forename: Balázs
authors.initials: B
authors.lastname: Gellén
authors.forename: Csaba
authors.initials: C
authors.lastname: Bereczki
authors.forename: Imre
authors.initials: I
authors.lastname: Ocsovszki
authors.forename: Judit
authors.initials: J
authors.lastname: Pipis
authors.forename: János
authors.initials: J
authors.lastname: Pálóczi
authors.forename: Márta
authors.initials: M
authors.lastname: Sárközy
authors.forename: Szilvia
authors.initials: S
authors.lastname: Török
authors.forename: Ilona S
authors.initials: IS
authors.lastname: Varga
authors.forename: István
authors.initials: I
authors.lastname: Kiss
authors.forename: Eszter
authors.initials: E
authors.lastname: Fodor
authors.forename: Tamás
authors.initials: T
authors.lastname: Csont
authors.forename: Péter
authors.initials: P
authors.lastname: Ferdinandy
authors.forename: Sándor
authors.initials: S
authors.lastname: Túri
mesh_terms: D000818:Animals; D000068256:Darbepoetin alfa; D004334:Drug Administration Schedule; D004921:Erythropoietin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005978:Glutathione / Q000097:blood*; D019803:Glutathione Disulfide / Q000097:blood*; D006397:Hematinics / Q000008:administration & dosage*; D008297:Male; D009392:Nephrectomy; D018384:Oxidative Stress; D051381:Rats
chemical_list: D006397:Hematinics; D004921:Erythropoietin; D000068256:Darbepoetin alfa; D005978:Glutathione; D019803:Glutathione Disulfide