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A Nitric Oxide-Donor Furoxan Moiety Improves the Efficacy of Edaravone against Early Renal Dysfunction and Injury Evoked by Ischemia/Reperfusion
by
Chegaev, Konstantin
, Chiazza, Fausto
, Fruttero, Roberta
, Lazzarato, Loretta
, Cutrin, Juan C.
, Rogazzo, Mara
, Benetti, Elisa
, Collino, Massimo
in
Acetylglucosamine - urine
/ Acute-Phase Proteins - urine
/ Animals
/ Antioxidants
/ Antipyrine - analogs & derivatives
/ Antipyrine - chemistry
/ Antipyrine - pharmacology
/ Creatinine - blood
/ Cytokines
/ Disease Models, Animal
/ Edaravone
/ Free Radical Scavengers - pharmacology
/ Free radicals
/ Ischemia
/ Ischemia - metabolism
/ Ischemia - pathology
/ Kidney - drug effects
/ Kidney - metabolism
/ Kidney - pathology
/ Kidneys
/ Laboratory animals
/ Lipid Peroxidation - drug effects
/ Lipocalins - urine
/ Male
/ Malondialdehyde - analysis
/ Mortality
/ Nitric oxide
/ Nitric Oxide Donors - chemistry
/ Nitric Oxide Donors - pharmacology
/ Oxadiazoles - chemistry
/ Oxadiazoles - pharmacology
/ Oxidative Stress - drug effects
/ Proto-Oncogene Proteins - urine
/ Proto-Oncogene Proteins c-akt - metabolism
/ Rats
/ Rats, Wistar
/ Reperfusion Injury - metabolism
/ Reperfusion Injury - pathology
/ Rodents
/ Studies
/ Urea - blood
/ Veins & arteries
2015
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A Nitric Oxide-Donor Furoxan Moiety Improves the Efficacy of Edaravone against Early Renal Dysfunction and Injury Evoked by Ischemia/Reperfusion
by
Chegaev, Konstantin
, Chiazza, Fausto
, Fruttero, Roberta
, Lazzarato, Loretta
, Cutrin, Juan C.
, Rogazzo, Mara
, Benetti, Elisa
, Collino, Massimo
in
Acetylglucosamine - urine
/ Acute-Phase Proteins - urine
/ Animals
/ Antioxidants
/ Antipyrine - analogs & derivatives
/ Antipyrine - chemistry
/ Antipyrine - pharmacology
/ Creatinine - blood
/ Cytokines
/ Disease Models, Animal
/ Edaravone
/ Free Radical Scavengers - pharmacology
/ Free radicals
/ Ischemia
/ Ischemia - metabolism
/ Ischemia - pathology
/ Kidney - drug effects
/ Kidney - metabolism
/ Kidney - pathology
/ Kidneys
/ Laboratory animals
/ Lipid Peroxidation - drug effects
/ Lipocalins - urine
/ Male
/ Malondialdehyde - analysis
/ Mortality
/ Nitric oxide
/ Nitric Oxide Donors - chemistry
/ Nitric Oxide Donors - pharmacology
/ Oxadiazoles - chemistry
/ Oxadiazoles - pharmacology
/ Oxidative Stress - drug effects
/ Proto-Oncogene Proteins - urine
/ Proto-Oncogene Proteins c-akt - metabolism
/ Rats
/ Rats, Wistar
/ Reperfusion Injury - metabolism
/ Reperfusion Injury - pathology
/ Rodents
/ Studies
/ Urea - blood
/ Veins & arteries
2015
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A Nitric Oxide-Donor Furoxan Moiety Improves the Efficacy of Edaravone against Early Renal Dysfunction and Injury Evoked by Ischemia/Reperfusion
by
Chegaev, Konstantin
, Chiazza, Fausto
, Fruttero, Roberta
, Lazzarato, Loretta
, Cutrin, Juan C.
, Rogazzo, Mara
, Benetti, Elisa
, Collino, Massimo
in
Acetylglucosamine - urine
/ Acute-Phase Proteins - urine
/ Animals
/ Antioxidants
/ Antipyrine - analogs & derivatives
/ Antipyrine - chemistry
/ Antipyrine - pharmacology
/ Creatinine - blood
/ Cytokines
/ Disease Models, Animal
/ Edaravone
/ Free Radical Scavengers - pharmacology
/ Free radicals
/ Ischemia
/ Ischemia - metabolism
/ Ischemia - pathology
/ Kidney - drug effects
/ Kidney - metabolism
/ Kidney - pathology
/ Kidneys
/ Laboratory animals
/ Lipid Peroxidation - drug effects
/ Lipocalins - urine
/ Male
/ Malondialdehyde - analysis
/ Mortality
/ Nitric oxide
/ Nitric Oxide Donors - chemistry
/ Nitric Oxide Donors - pharmacology
/ Oxadiazoles - chemistry
/ Oxadiazoles - pharmacology
/ Oxidative Stress - drug effects
/ Proto-Oncogene Proteins - urine
/ Proto-Oncogene Proteins c-akt - metabolism
/ Rats
/ Rats, Wistar
/ Reperfusion Injury - metabolism
/ Reperfusion Injury - pathology
/ Rodents
/ Studies
/ Urea - blood
/ Veins & arteries
2015
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A Nitric Oxide-Donor Furoxan Moiety Improves the Efficacy of Edaravone against Early Renal Dysfunction and Injury Evoked by Ischemia/Reperfusion
Journal Article
A Nitric Oxide-Donor Furoxan Moiety Improves the Efficacy of Edaravone against Early Renal Dysfunction and Injury Evoked by Ischemia/Reperfusion
2015
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Overview
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.
Publisher
Hindawi Publishing Corporation,John Wiley & Sons, Inc
Subject
/ Acute-Phase Proteins - urine
/ Animals
/ Antipyrine - analogs & derivatives
/ Free Radical Scavengers - pharmacology
/ Ischemia
/ Kidneys
/ Lipid Peroxidation - drug effects
/ Male
/ Nitric Oxide Donors - chemistry
/ Nitric Oxide Donors - pharmacology
/ Oxidative Stress - drug effects
/ Proto-Oncogene Proteins - urine
/ Proto-Oncogene Proteins c-akt - metabolism
/ Rats
/ Reperfusion Injury - metabolism
/ Reperfusion Injury - pathology
/ Rodents
/ Studies
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