title: Effectiveness of a single versus repeated administration of trimetazidine in the protection against warm ischemia/reperfusion injury of rat liver.
abstract: OBJECTIVE
  The aim of this study was to compare the effects of single and repeated trimetazidine (TMZ) administration against warm hepatic ischemia/reperfusion (I/R) injury and to explore the possible mechanisms affected by TMZ.
  
  
  METHODS
  Wistar rats were divided into 4 groups (n = 6). Sham: rats were subjected to dissection. I/R: rats were subjected to 60 min of partial hepatic ischemia followed by 24 h of reperfusion. TMZ1: Same as I/R group but rats were pretreated with a single dose of TMZ (10 mg/kg, intraperitoneal injection) 30 min before warm ischemia. TMZ3: Same as I/R but rats were treated with 10 mg/kg TMZ for 3 successive days.
  
  
  RESULTS
  TMZ treatment decreased liver injury, lipid peroxidation, and apoptosis. The repeated administration of TMZ conferred more protection than the single dose treatment concerning all studied parameters. In parallel, we noted a significant increase in phosphorylated adenosine monophosphate activated protein kinase (p-AMPK) and endothelial nitric oxide synthase (eNOS) levels in TMZ3 as compared to TMZ1.
  
  
  CONCLUSIONS
  Repeated administration of TMZ for 3 days was more efficient than a single dose of TMZ in protecting the liver against I/R induced apoptosis and lipid peroxidation. These effects implicate AMPK and eNOS activation.
authors: Laboratory of Physiology, Research Unit "UR12ES11", Faculty of Pharmacy, University of Monastir, Tunisia.
authors: Asma
authors: A
authors: Mahfoudh Boussaid
authors: Laboratory of Physiology, Research Unit "UR12ES11", Faculty of Pharmacy, University of Monastir, Tunisia.
authors: Rabi
authors: R
authors: Selmi
authors: Hepatic Ischemia Reperfusion Unit, Department of Experimental Pathology, Institut d'Investigaciones Biomèdiques de Barcelona Consejo Superior de Investigaciones Científicas, Barcelona, Spain.
authors: Mohamed
authors: M
authors: Bejaoui
authors: Laboratory of Physiology, Research Unit "UR12ES11", Faculty of Pharmacy, University of Monastir, Tunisia.
authors: Kaouther
authors: K
authors: Hadj Ayed
authors: Laboratory of Physiology, Research Unit "UR12ES11", Faculty of Pharmacy, University of Monastir, Tunisia.
authors: Mohamed Amine
authors: MA
authors: Zaouali
authors: Laboratory of Physiology, Research Unit "UR12ES11", Faculty of Pharmacy, University of Monastir, Tunisia.
authors: Hassen
authors: H
authors: Ben Abdennebi
mesh_terms: D000818:Animals; D008099:Liver; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury; D014292:Trimetazidine; D052096:Warm Ischemia
chemical_list: D014292:Trimetazidine
keywords: Ischemia/reperfusion injury; adenosine monophosphate activated protein kinase; apoptosis; endothelial nitric oxide synthase; liver; trimetazidine