Etomidate Inhibits Hepatic Ischemia-Reperfusion Injury Depending on the Activation of Nrf2-HO-1 Signaling Pathway.

Abstract

Hepatic ischemia-reperfusion (I/R) injury (HIRI) is recognized as a local aseptic inflammatory response driven by innate immunity and is considered a leading cause of early organ dysfunction and failure following liver transplantation. Etomidate (Eto), an anesthetic drug known for its ability to inhibit inflammatory response and apoptosis, was the focus of our investigation. In this study, we conducted hepatic I/R surgery invivo on C57 mice, analyzing liver damage through histopathology. Additionally, primary hepatocytes isolated from mice were cultured and subjected to hypoxia/reoxygenation (H/R) insult in vitro, with cell activity assessed using the CCK8 assay and immunofluorescence staining employed to analyze liver inflammatory cell infiltration and apoptosis. Results showed that Eto effectively inhibited liver injury, inflammatory response, and apoptosis induced by HIRI surgery, with the greatest effect observed at an Eto concentration of 10 mg/kg. Furthermore, Eto also showed the ability to inhibit H/R-induced cell damage, inflammatory activation, and apoptosis in primary hepatocytes. Further mechanistic studies revealed that Eto could promote the activation of the Nrf2-HO-1 signaling pathway, and the protective effect of Eto on HIRI was nullified when the Nrf2 inhibitor ML385 was utilized. This study highlights the potential of Eto to protect against HIRI by promoting the Nrf2-HO-1 signaling axis.