Abstract
Scutellarin is a natural flavonoid that has been found to exhibit anti-ischemic effect. However, the effect of scutellarin on hepatic hypoxia/reoxygenation (ischemia–reperfusion (I/R)) injury remains unknown. The aim of the present study was to explore the protective effect of scutellarin on I/R-induced injury in hepatocytes. Our results showed that scutellarin improved cell viability in hepatocytes exposed to hypoxia/reoxygenation (H/R). Scutellarin treatment resulted in decreased levels of reactive oxygen species (ROS) and malondialdehyde (MDA), and increased superoxide dismutase (SOD) activity in H/R-induced hepatocytes. In addition, scutellarin reduced cell apoptosis in H/R-stimulated hepatocytes, as proved by the decreased apoptotic rate. Moreover, scutellarin significantly up-regulated bcl-2 expression and down-regulated bax expression in hepatocytes exposed to H/R. Furthermore, scutellarin treatment caused significant decrease in Keap1 expression and increase in nuclear Nrf2 expression. Besides, scutellarin induced the mRNA expressions of heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO1). Inhibition of Nrf2 significantly reversed the protective effects of scutellarin on H/R-stimulated hepatocytes. In conclusion, these findings demonstrated that scutellarin protected hepatocytes from H/R-induced oxidative injury through regulating the Keap1/Nrf2/ARE signaling pathway, indicating a potential relevance of scutellarin in attenuating hepatic I/R injury.
Highlights
Hepatic ischemia–reperfusion (I/R) injury is a commonly identified clinical complication that frequently occurs after liver transplantation, liver resection, stroke, and trauma, which may result in organ dysfunction and failure [1,2]
Scutellarin improved the viability of hepatocytes in response to H/R
The results indicated that scutellarin at the concentration of 80 μM caused a significant inhibition of the viability of hepatocytes
Summary
Hepatic ischemia–reperfusion (I/R) injury is a commonly identified clinical complication that frequently occurs after liver transplantation, liver resection, stroke, and trauma, which may result in organ dysfunction and failure [1,2]. It is generally believed that I/R injury is negatively associated with the survival rate and prognosis of the patients. During the process of hepatic I/R injury, cellular hypoxia and reoxygenation are two essential elements [4]. Excess production of reactive oxygen species (ROS) is considered as a critical factor in the genesis of reperfusion injury. The imbalance between the rate of generation of ROS and the ability to detoxify ROS may lead to oxidative stress and evoke acute inflammatory response that will further aggravate hepatocellular injury [5]. Considerable efforts have been devoted to developing effective agents for blocking the sources of excess ROS production [6]
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