A Nitric Oxide-Donor Furoxan Moiety Improves the Efficacy of Edaravone against Early Renal Dysfunction and Injury Evoked by IschemiaReperfusion
Joint Authors
Collino, Massimo
Rogazzo, Mara
Benetti, Elisa
Chegaev, Konstantin
Cutrin, Juan C.
Lazzarato, Loretta
Fruttero, Roberta
Chiazza, Fausto
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2015, Issue 2015 (31 Dec. 2015), pp.1-12, 12 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2015-03-05
Country of Publication
Egypt
No. of Pages
12
Main Subjects
Abstract EN
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.
American Psychological Association (APA)
Chiazza, Fausto& Chegaev, Konstantin& Rogazzo, Mara& Cutrin, Juan C.& Benetti, Elisa& Lazzarato, Loretta…[et al.]. 2015. A Nitric Oxide-Donor Furoxan Moiety Improves the Efficacy of Edaravone against Early Renal Dysfunction and Injury Evoked by IschemiaReperfusion. Oxidative Medicine and Cellular Longevity،Vol. 2015, no. 2015, pp.1-12.
https://search.emarefa.net/detail/BIM-1075783
Modern Language Association (MLA)
Chiazza, Fausto…[et al.]. A Nitric Oxide-Donor Furoxan Moiety Improves the Efficacy of Edaravone against Early Renal Dysfunction and Injury Evoked by IschemiaReperfusion. Oxidative Medicine and Cellular Longevity No. 2015 (2015), pp.1-12.
https://search.emarefa.net/detail/BIM-1075783
American Medical Association (AMA)
Chiazza, Fausto& Chegaev, Konstantin& Rogazzo, Mara& Cutrin, Juan C.& Benetti, Elisa& Lazzarato, Loretta…[et al.]. A Nitric Oxide-Donor Furoxan Moiety Improves the Efficacy of Edaravone against Early Renal Dysfunction and Injury Evoked by IschemiaReperfusion. Oxidative Medicine and Cellular Longevity. 2015. Vol. 2015, no. 2015, pp.1-12.
https://search.emarefa.net/detail/BIM-1075783
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1075783