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dc.contributor.author
Chiazza, Fausto
dc.contributor.author
Chegaev, Konstantin
dc.contributor.author
Rogazzo, Mara
dc.contributor.author
Cutrin, Juan Carlos
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dc.contributor.author
Beneti, Elisa
dc.contributor.author
Lazzarato, Loretta
dc.contributor.author
Fruttero, Roberta
dc.contributor.author
Collino, Massimo
dc.date.available
2016-11-01T21:26:54Z
dc.date.issued
2015-05
dc.identifier.citation
Chiazza, Fausto; Chegaev, Konstantin; Rogazzo, Mara; Cutrin, Juan Carlos; Beneti, Elisa; et al.; A Nitric Oxide-Donor Furoxan Moiety Improves the Efficacy of Edaravone against Early Renal Dysfunction and Injury Evoked by Ischemia/Reperfusion; Landes Bioscience; Oxidative Medicine And Cellular Longevity; 2015; 5-2015; 1-12
dc.identifier.issn
1942-0900
dc.identifier.uri
http://hdl.handle.net/11336/7911
dc.description.abstract
Edaravone (5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one, EDV) is a free-radical scavenger reduces organ ischemic injury. Here we investigated whether the protective effects of EDV in renal ischemia/reperfusion (I/R) injury may be enhanced by an EDV derivative bearing a nitric oxide- (NO-) donor furoxan moiety (NO-EDV). Male Wistar rats were subjected to renal ischemia (45 minutes), followed by reperfusion (6 hours). Administration of either EDV (1.2–6–30 µmol/kg, i.v.) or NO-EDV (0.3–1.2–6 µmol/kg, i.v.) dose-dependently attenuated markers of renal dysfunction (serum urea and creatinine, creatinine clearance, urine flow, urinary N-acetyl-β-D-glucosaminidase, and neutrophil gelatinase-associated lipocalin/lipocalin-2). NO-EDV exerted protective effects in the dose-range 1.2–6 µmol/kg, while a higher dose (30 µmol/kg) was needed to obtain protection by EDV. Both EDV and NO-EDV modulated tissue markers of oxidative stress and lipid peroxidation. NO-EDV, but not EDV, activated endothelial NO synthase (NOS) and blunted I/R-induced upregulation of inducible NOS, secondary to modulation of Akt and NF-κB activation, respectively. Besides NO-EDV administration inhibited I/R-induced IL-1β, IL-18, IL-6, and TNF-α overproduction. Overall, these findings demonstrate that the NO-donor moiety contributes to the protection against early renal I/R injury and suggest that NO-donor EDV codrugs are worthy of additional study as innovative pharmacological tools.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Landes Bioscience
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dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by/2.5/ar/
dc.subject
Nitric Oxide Donor
dc.subject
Kidney Ischemia-Reperfusion
dc.subject.classification
Farmacología y Farmacia
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dc.subject.classification
Medicina Básica
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dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
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dc.title
A Nitric Oxide-Donor Furoxan Moiety Improves the Efficacy of Edaravone against Early Renal Dysfunction and Injury Evoked by Ischemia/Reperfusion
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2016-08-30T17:11:48Z
dc.identifier.eissn
1942-0994
dc.journal.volume
2015
dc.journal.pagination
1-12
dc.journal.pais
Estados Unidos
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dc.journal.ciudad
Austin
dc.description.fil
Fil: Chiazza, Fausto. Universitã â Di Torino; Italia
dc.description.fil
Fil: Chegaev, Konstantin. Università  Di Torino; Italia
dc.description.fil
Fil: Rogazzo, Mara. Universitã â Di Torino; Italia
dc.description.fil
Fil: Cutrin, Juan Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Cardiológicas (i); Argentina
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Fil: Beneti, Elisa. Universita di Torino; Italia
dc.description.fil
Fil: Lazzarato, Loretta. Universita di Torino; Italia
dc.description.fil
Fil: Fruttero, Roberta. Universita di Torino; Italia
dc.description.fil
Fil: Collino, Massimo. Universita di Torino; Italia
dc.journal.title
Oxidative Medicine And Cellular Longevity
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dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.hindawi.com/journals/omcl/2015/804659/
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1155/2015/804659
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4365375/
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