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

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.

Propofol Attenuated Acute Kidney Injury after Orthotopic Liver Transplantation via Inhibiting Gap Junction Composed of Connexin 32

“…17,18 Initially, we used an open face guard to administer the inhalational ether anesthesia until the rats had no response to a needle stimulus. Rat AOLT models were established as previously described.…”

SERPINB1 ameliorates acute lung injury in liver transplantation through ERK1/2-mediated STAT3-dependent HO-1 induction

“…We previously showed that induction of HO-1 by anesthetic propofol or HO-1 inducer hemin, through inhibiting inflammation and oxidative stress, ameliorated ALI in rats with orthotopic autologous liver transplantation (OALT) [4][5][6][7][8] . However, the mechanism governing HO-1 induction in post-LT ALI remains unclear.…”

Propofol Prevents Renal Ischemia-Reperfusion Injury via Inhibiting the Oxidative Stress Pathways

“…In addition to its use for maintenance of sedative effects as an anesthetic, propofol shows effectiveness in anti-oxidative, antiemetic and anti-anxiety activities [34]. Some studies have found the protective effects of propofol on myocardial ischemia, lipopolysaccharide-induced acute lung injury, and brain slice injury associated with its antioxidant properties and reducing intracellular calcium [35][36][37][38]. Propofol also has renoprotective effects on renal injury via inhibiting gap junction composed of connexin 32 [39].…”