The effects of meldonium on the acute ischemia/reperfusion liver injury in rats

Abstract

Acute ischemia/reperfusion (I/R) liver injury is a clinical condition challenging to treat. Meldonium is an anti‑ischemic agent that shifts energy production from fatty acid oxidation to less oxygen‑ consuming glycolysis. Thus, we investigated the effects of a 4‑week meldonium pre‑treatment (300 mg/kg b.m./day) on the acute I/R liver injury in Wistar strain male rats. Our results showed that meldonium ameliorates I/R‑induced liver inflammation and injury, as confirmed by liver histology, and by attenuation of serum alanine‑ and aspartate aminotransferase activity, serum and liver high mobility group box 1 protein expression, and liver expression of Bax/Bcl2, haptoglobin, and the phosphorylated nuclear factor kappa‑light‑chain‑enhancer of activated B cells. Through the increased hepatic activation of the nuclear factor erythroid 2‑related factor 2, meldonium improves the antioxidative defence in the liver of animals subjected to I/R, as proved by an increase in serum and liver ascorbic/dehydroascorbic acid ratio, hepatic haem oxygenase 1 expression, glutathione and free thiol groups content, and hepatic copper‑zinc superoxide dismutase, manganese superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase activity. Based on our results, it can be concluded that meldonium represent a protective agent against I/R‑induced liver injury, with a clinical significance in surgical procedures.