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Drug Metabolism and Personalized Therapy

Official journal of the European Society of Pharmacogenomics and Personalised Therapy

Editor-in-Chief: Llerena, Adrián

Editorial Board: Benjeddou, Mongi / Chen, Bing / Dahl, Marja-Liisa / Devinsky, Ferdinand / Hirata, Rosario / Hubacek, Jaroslav A. / Ingelman-Sundberg, Magnus / Maitland-van der Zee, Anke-Hilse / Manolopoulos, Vangelis G. / Marc, Janja / Melichar, Bohuslav / Meyer, Urs A. / Nair, Sujit / Nofziger, Charity / Peiro, Ana / Sadee, Wolfgang / Salazar, Luis A. / Simmaco, Maurizio / Turpeinen, Miia / Schaik, Ron / Shin, Jae-Gook / Visvikis-Siest, Sophie / Zanger, Ulrich M.


CiteScore 2018: 1.01

SCImago Journal Rank (SJR) 2018: 0.277
Source Normalized Impact per Paper (SNIP) 2018: 0.446

Online
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2363-8915
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Volume 26, Issue 2

Issues

Experimental evidence of the potential use of erythropoietin by intranasal administration as a neuroprotective agent in cerebral hypoxia

Amalia Merelli
  • Instituto de Biología Celular y Neurociencias “Prof. E. de Robertis”, Facultad de Medicina, UBA-CONICET, Buenos Aires, Argentina
  • Instituto de Investigaciones en Fisiopatología y Bioquímica Clínica (INFIBIOC), Facultad de Farmacia y Bioquímica, UBA, Buenos Aires, Argentina
  • A.M., L.C., A.L., and A.B. are members of GENIAR (CYTED #610RT0405).
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  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Laura Caltana
  • Instituto de Biología Celular y Neurociencias “Prof. E. de Robertis”, Facultad de Medicina, UBA-CONICET, Buenos Aires, Argentina
  • A.M., L.C., A.L., and A.B. are members of GENIAR (CYTED #610RT0405).
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Alberto Lazarowski
  • Instituto de Biología Celular y Neurociencias “Prof. E. de Robertis”, Facultad de Medicina, UBA-CONICET, Buenos Aires, Argentina
  • Instituto de Investigaciones en Fisiopatología y Bioquímica Clínica (INFIBIOC), Facultad de Farmacia y Bioquímica, UBA, Buenos Aires, Argentina
  • A.M., L.C., A.L., and A.B. are members of GENIAR (CYTED #610RT0405).
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Alicia Brusco
  • Instituto de Biología Celular y Neurociencias “Prof. E. de Robertis”, Facultad de Medicina, UBA-CONICET, Buenos Aires, Argentina
  • A.M., L.C., A.L., and A.B. are members of GENIAR (CYTED #610RT0405).
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2011-07-14 | DOI: https://doi.org/10.1515/dmdi.2011.007

Abstract

Stroke is a major human health problem without efficient available therapeutics. Ischemic brain injury can induce cell death as well as upregulation of endogenous adaptive mechanisms depending on the severity and duration of hypoxia, and the activity of transcription factors, such as hypoxia inducible factor 1-α (HIF-1α). HIF-1α induces gene expression as multidrug resistance (MDR-1) gene associated with drug-refractory phenotype, as well as erythropoietin (Epo) and erythropoietin receptor (Epo-R) associated with O2 supply. The spontaneous stimulation of the Epo/Epo-R system is not enough for brain protection. Therefore, administration of exogenous recombinant human Epo (rHu-Epo) was suggested as an alternative therapy in stroke. In several experimental models of brain hypoxia, Epo and Epo variants, including rHu-Epo, showed neuroprotective effects. Intranasal administration of these Epo-compounds can reach the central nervous system and protect the brain against ischemia, avoiding hematopoietic effects. However, it has been reported that high expression of Epo-R in neurons must be available to be activated by Epo. According to these considerations, intranasal delivery of rHu-Epo could be an interesting approach in the treatment of cerebral hypoxias avoiding both (i) adverse peripheral effects of treatment with Epo in stroke, and (ii) the pharmacoresistant phenotype depending on MDR-1 expression.

Keywords: erythropoietin; hypoxia inducible factor 1-α (HIF-1α); intranasal delivery; multidrug resistance (MDR-1) gene; neuroprotection; stroke

About the article

Corresponding author: Amalia Merelli, Instituto de Biología Celular y Neurociencias “Prof. E. de Robertis”, Facultad de Medicina, UBA-CONICET, Calle Paraguay 2155, 3er piso, C1121ABG Buenos Aires, Argentina


Received: 2011-02-22

Accepted: 2011-06-10

Published Online: 2011-07-14

Published Online: 2011-07-14

Published in Print: 2011-08-01


Citation Information: Drug Metabolism and Drug Interactions, Volume 26, Issue 2, Pages 65–69, ISSN (Online) 2191-0162, ISSN (Print) 0792-5077, DOI: https://doi.org/10.1515/dmdi.2011.007.

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