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.
Ischemia/reperfusion injury, liver, trimetazidine, adenosine monophosphate activated protein kinase, endothelial nitric oxide synthase, apoptosis
BOUSSAID, ASMA MAHFOUDH; SELMI, RABI; BEJAOUI, MOHAMED; AYED, KAOUTHER HADJ; ZAOUALI, MOHAMED AMINE; and ABDENNEBI, HASSEN BEN
"Effectiveness of a single versus repeated administration of trimetazidine in the protection against warm ischemia/reperfusion injury of rat liver,"
Turkish Journal of Medical Sciences: Vol. 46:
4, Article 46.
Available at: https://journals.tubitak.gov.tr/medical/vol46/iss4/46