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Effects of trimetazidine on the Akt/eNOS signaling pathway and oxidative stress in an in vivo rat model of renal ischemia-reperfusion
- Source :
- Digital.CSIC. Repositorio Institucional del CSIC, instname
- Publication Year :
- 2014
-
Abstract
- © 2014 Informa Healthcare USA, Inc. All rights reserved. Renal ischemia reperfusion (I/R) injury, which occurs during renal surgery or transplantation, is the major cause of acute renal failure. Trimetazidine (TMZ), an anti-ischemic drug, protects kidney against the deleterious effects of I/R. However its protective mechanism remains unclear. The aim of this study is to examine the relevance of Akt, endothelial nitric oxide synthase (eNOS), and hypoxia inducible factor-1α (HIF-1α) on TMZ induced protection of kidneys against I/R injury. Wistar rats were subjected to 60 min of warm renal ischemia followed by 120 min of reperfusion, or to intraperitoneal injection of TMZ (3 mg/kg) 30 min before ischemia. In sham operated group renal pedicles were only dissected. Compared to I/R, TMZ treatment decreased lactate dehydrogenase (845 ± 13 vs. 1028 ± 30 U/L). In addition, creatinine clearance and sodium reabsorption rates reached 105 ± 12 versus 31 ± 11 μL/min/g kidney weight and 95 ± 1 versus 68 ± 5%, respectively. Besides, we noted a decrease in malondialdehyde concentration (0.33 ± 0.01 vs. 0.59 ± 0.03 nmol/mg of protein) and an increase in glutathione concentration (2.6 ± 0.2 vs. 0.93 ± 0.16 μg GSH/mg of protein), glutathione peroxidase (95 ± 4 vs. 61 ± 3 μg GSH/min/mg of protein), and superoxide dismutase (25 ± 3 vs. 11 ± 2 U/mg of protein) and catalase (91 ± 12 vs. 38 ± 9 μmol/min/mg of protein) activities. Parallely, we noted a significant increase in p-Akt, eNOS, nitrite and nitrate (18 ± 2 vs. 8 ± 0.1 pomL/mg of protein), HIF-1α (333 ± 48 vs. 177 ± 14 μg/mg of protein) and heme oxygenase-1 (HO-1) levels regarding I/R. TMZ treatment improves renal tolerance to warm I/R. Such protection implicates an activation of Akt/eNOS signaling pathway, HIF-1α stabilization and HO-1 activation.
- Subjects :
- Male
Nitric Oxide Synthase Type III
Vasodilator Agents
Blotting, Western
Trimetazidine
Ischemia
Renal function
Ischemia/reperfusion
Pharmacology
Critical Care and Intensive Care Medicine
Kidney
Enos
medicine
Animals
Rats, Wistar
Renal sodium reabsorption
Renal ischemia
biology
business.industry
General Medicine
biology.organism_classification
medicine.disease
Hypoxia-Inducible Factor 1, alpha Subunit
Rats
Transplantation
Oxidative Stress
medicine.anatomical_structure
Nephrology
Oxidative stress
Anesthesia
Reperfusion Injury
Kidney Diseases
business
Proto-Oncogene Proteins c-akt
Heme Oxygenase-1
medicine.drug
Signal Transduction
Subjects
Details
- ISSN :
- 15256049
- Volume :
- 36
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Renal failure
- Accession number :
- edsair.doi.dedup.....d6b15a90c223c45ce92111de4be89fa6