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Effectiveness of a single versus repeated administration of trimetazidine in the protection against warm ischemia/reperfusion injury of rat liver

AuthorsMahfoudh Boussaid, Asma; Selmi, Rabi; Bejaoui, Mohamed ; Hadj Ayed, Kaouther; Zaouali, Mohamed A. ; Ben Abdennebi, Hassen
Endothelial nitric oxide synthase
Adenosine monophosphate activated protein kinase
Ischemia/reperfusion injury
Issue Date23-Jun-2016
PublisherScientific and Technological Research Council of Turkey
CitationTurkish Journal of Medical Sciences 46: 1258-1264 (2016)
Abstract[Background/aim] 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. [Materials and 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. [Conclusion] 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.
Publisher version (URL)https://doi.org/10.3906/sag-1505-102
Identifiersdoi: 10.3906/sag-1505-102
issn: 1300-0144
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