Propofol Activation of the Nrf2 Pathway Is Associated with Amelioration of Acute Lung Injury in a Rat Liver Transplantation Model

Weifeng Yao,Ziqing Hei,Zhengyuan Xia,Gangjian Luo,Guosong Zhu,Xinjin Chi,Ailan Zhang

doi:10.1155/2014/258567

Abstract

Objective. This study aimed to investigate whether propofol pretreatment can protect against liver transplantation-induced acute lung injury (ALI) and to explore whether Nrf2 pathway is involved in the protections provided by propofol pretreatment. Method. Adult male Sprague-Dawley rats were divided into five groups based on the random number table. Lung pathology was observed by optical microscopy. Lung water content was assessed by wet/dry ratio, and PaO2 was detected by blood gas analysis. The contents of H2O2, MDA, and SOD activity were determined by ELISA method, and the expression of HO-1, NQO1, Keap1, and nuclear Nrf2 was assayed by western blotting. Results. Compared with saline-treated model group, both propofol and N-acetylcysteine pretreatment can reduce the acute lung injury caused by orthotopic autologous liver transplantation (OALT), decrease the lung injury scores, lung water content, and H2O2 and MDA levels, and improve the arterial PaO2 and SOD activity. Furthermore, propofol (but not N-acetylcysteine) pretreatment especially in high dose inhibited the expression of Keap1 and induced translocation of Nrf2 into the nucleus to further upregulate the expression of HO-1 and NQO1 downstream. Conclusion. Pretreatment with propofol is associated with attenuation of OALT-induced ALI, and the Nrf2 pathway is involved in the antioxidative processes.

Highlights

acute lung injury (ALI) occurs after orthotopic liver transplantation (OLT) in approximately 34.2% to 77.8% of cases [1, 2]
The main findings of the present experiments were that propofol reduced the decline in oxygenation, pulmonary edema, reactive oxygen species (H2O2) and lipid peroxidation (MDA), and histologic alteration induced by orthotopic autologous liver transplantation (OALT) through the Nrf2 antioxidant response pathway
To the best of our knowledge, this is the first report showing that the antioxidant pathway mediated by Nrf2 is associated with protective effect of propofol (Figure 6) in ALI induced by liver transplantation

Summary

Introduction

ALI occurs after orthotopic liver transplantation (OLT) in approximately 34.2% to 77.8% of cases [1, 2]. Some studies have suggested that inflammation is the main mechanism and therapeutic target of ALI induced by liver transplantation [4,5,6,7,8]. Recent studies have shown that oxidative stress is another important pathogenic mechanism of ALI [9]. The status of oxidative stress in, and effects of antioxidant therapy on ALI induced by liver transplantation are poorly understood. Recent studies have suggested that propofol takes part in protection of various organs during acute injury. HO-1 has been reported to be involved in the antioxidative mechanism of propofol [15,16,17,18]

Methods

Results

Conclusion