title: "Effects of recombinant human erythropoietin high mimicking abuse doses on oxidative stress processes in rats".
abstract: Although many studies highlight how long-term moderate dose of Recombinant Human Erythropoietin (rHuEPO) treatments result in beneficial and antioxidants effects, few studies take into account the effects that short-term high doses of rHuEPO (mimicking abuse conditions) might have on the oxidative stress processes. Thus, the aim of this study was to investigate the in vivo antioxidant activity of rHuEPO, administered for a short time and at high doses to mimic its sports abuse as doping. Male Wistar healthy rats (n=36) were recruited for the study and were treated with three different concentrations of rHuEPO: 7.5, 15, 30μg/kg. Plasma concentrations of erythropoietin, 8-epi Prostaglandin F2α, plasma and urinary concentrations of NOx were evaluated with specific assay kit, while hematocrit levels were analyzed with an automated cell counter. Antioxidant activity of rHuEPO was assessed analyzing the possible variation of the plasma scavenger capacity against hydroxylic and peroxylic radicals by TOSC (Total Oxyradical Scavenging Capacity) assay. Statistical analyses showed higher hematocrit values, confirmed by a statistically significant increase of plasmatic EPO concentration. An increase in plasma scavenging capacity against peroxyl and hydroxyl radicals, in 8-isoprostane plasmatic concentrations and in plasmatic and urinary levels of NOX were also found in all the treated animals, though not always statistically significant. Our results confirm the literature data regarding the antioxidant action of erythropoietin administered at low doses and for short times, whereas they showed an opposite incremental oxidative stress action when erythropoietin is administered at high doses.
authors.affiliation: Department of Translational Research and New Technologies in Medicine and Surgery, Pharmacology, Medical School, University of Pisa, Via Roma 55, 56126, Pisa, Italy. Electronic address: sara.bianchi1987@hotmail.it.
authors.forename: Sara
authors.initials: S
authors.lastname: Bianchi
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Via Savi 10, 56126, Pisa, Italy.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Fusi
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Via Savi 10, 56126, Pisa, Italy.
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Franzoni
authors.affiliation: Department of Translational Research and New Technologies in Medicine and Surgery, Pharmacology, Medical School, University of Pisa, Via Roma 55, 56126, Pisa, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Giovannini
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Via Savi 10, 56126, Pisa, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Galetta
authors.affiliation: Department of Translational Research and New Technologies in Medicine and Surgery, Pharmacology, Medical School, University of Pisa, Via Roma 55, 56126, Pisa, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Mannari
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Via Savi 10, 56126, Pisa, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Guidotti
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Via Savi 10, 56126, Pisa, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Tocchini
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Via Savi 10, 56126, Pisa, Italy.
authors.forename: Gino
authors.initials: G
authors.lastname: Santoro
mesh_terms: D000818:Animals; D015237:Dinoprost / Q000031:analogs & derivatives / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004921:Erythropoietin / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000378:metabolism; D006400:Hematocrit; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D009566:Nitrates / Q000097:blood / Q000652:urine; D009573:Nitrites / Q000097:blood / Q000652:urine; D018384:Oxidative Stress / Q000187:drug effects*; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: C554270:EPO protein, human; D016166:Free Radical Scavengers; D009566:Nitrates; D009573:Nitrites; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D004921:Erythropoietin; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost
keywords: Erythropoietin; Free radicals; Hydroxyl radicals; Peroxyl radicals; Peroxynitrite