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

摘要

[Background/aim] The aim of this study was to compare the effects of single and repeated trimetazidine (TMZ) administration against\udwarm hepatic ischemia/reperfusion (I/R) injury and to explore the possible mechanisms affected by TMZ.\ud\ud[Materials and methods] Wistar rats were divided into 4 groups (n = 6). Sham: rats were subjected to dissection. I/R: rats were subjected\udto 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\uddose of TMZ (10 mg/kg, intraperitoneal injection) 30 min before warm ischemia. TMZ3: Same as I/R but rats were treated with 10 mg/\udkg TMZ for 3 successive days.\ud\ud[Results] TMZ treatment decreased liver injury, lipid peroxidation, and apoptosis. The repeated administration of TMZ conferred\udmore protection than the single dose treatment concerning all studied parameters. In parallel, we noted a significant increase in\udphosphorylated adenosine monophosphate activated protein kinase (p-AMPK) and endothelial nitric oxide synthase (eNOS) levels in\udTMZ3 as compared to TMZ1.\ud\ud[Conclusion] Repeated administration of TMZ for 3 days was more efficient than a single dose of TMZ in protecting the liver against I/R\udinduced apoptosis and lipid peroxidation. These effects implicate AMPK and eNOS activation.