Figure 3.
The summarised effects of meldonium pre-treatment on the liver ischemia/reperfusion. Meldonium pre-treatment improves the antioxidative defence through the increased hepatic activation of the nuclear factor erythroid 2-related factor 2 (p-Nrf2) and consequently hepatic haem oxygenase 1 (HO-1) expression, and activity of endogenous antioxidant enzymes. Thereby inhibits oxidative burst, tissue injury and cell necrosis, manifested by decreased expression of serum and liver high mobility group box 1 (HMGB1). Meldonium also reduces inflammatory cascade, as evident by decreased activation of the nuclear factor kappa-light-chain-enhancer of activated B cells (p-NF-kB p65) by phosphorylation along with decreased haptoglobin (Hp) expression. Simultaneously, meldonium attenuates apoptosis by decreasing the ratio of pro-apoptotic Bax and anti-apoptotic Bcl-2.