Sevoflurane suppresses oxidation-induced stress and inflammatory responses, via promotion of Nrf2-induced antioxidant signaling

Abstract

This study aimed to investigate the role of sevoflurane on anti-oxidant effects in sepsis-induced multiple organ failure. Western blot and quantitative RT–PCR were used to measure the expression of Nrf2 and its downstream genes. The DCFH-DA fluorescence probe assay was performed to assess the intracellular levels in HUVECs and LMVECs. Electrophoretic mobility shift assay was used to assess the DNA binding activities of Nrf2. Better survival, reduced expression of inflammatory cytokines, and improved pathological infiltration in the lungs and kidneys were observed in septic rats treated with sevoflurane. SOD activity increased and Nrf2–ARE signaling pathway was activated following sevoflurane treatment. The protective effect was lost in sepsis-induced acute lung injury (ALI) following inhibition of Nrf2 by intratracheal delivery of siRNA-Nrf2. In vitro experiments, we found the sevoflurane could suppress ROS production after stimulation with LPS and the application of sevoflurane augments the DNA-binding activity of Nrf2 in HUVECs and LMVECs. However, knockdown of Nrf2 by siRNA-Nrf2, the Protein kinase C (PKC) inhibitor, and the Nrf2 inhibitor ML385 could partially recover ROS production, inhibit the activity of SOD, and repress the expression of anti-oxidant genes following sevoflurane treatment. Sevoflurane could have protective effects in ALI and septic multiple organ disorders (MODs).