Propofol alleviates acute lung injury following orthotopic autologous liver transplantation in rats via inhibition of the NADPH oxidase pathway

Abstract

Abstract. Acute lung injury (ALI) induced by liver transplantation is detrimental to patient survival, and therapeutic strategies remain limited. Thus, the protective effects of propofol, a commonly used anesthetic with antioxidative and anti-inflammatory properties, were investigated in the present study on ALI induced by orthotopic autologous liver transplantation (OALT). The protective mechanism of propofol was determined to be associated with the inhibition of NADPH oxidase, by comparing its effects with the positive controls apocynin (AP; an NADPH oxidase inhibitor) and N-acegysteine (NAC; a scavenger of reactive oxygen species). The results demonstrated that two proteins (p47phox and gp91phox) of the NADPH oxidase system presented increased expression in rats with ALI induced by OALT, thus leading to increased activation of the oxidative stress and inflammatory reactions. Preconditioning with NAC or AP eliminated this increase, suggesting that antioxidative treatment, particularly with inhibitors of NADPH oxidase, is a promising protective strategy against ALI induced by OALT. Propofol preconditioning at a high (100 mg/kg) or low (50 mg/kg) dose promoted similar protective effects, with the high-dose propofol producing a more marked effect than the low dose. The results suggested that propofol may protect against ALI induced by OALT, the mechanism of which may involve a reduced oxidative stress and inflammatory reaction mediated by NADPH oxidase inhibition.

Propofol attenuated liver transplantation-induced acute lung injury via connexin43 gap junction inhibition

“…Rat AOLT model was established to explore effects of liver transplantation on lungs. ALI was most serious at 8 h after AOLT which was the same as our previous study [ 5 ]. In AOLT model group, alveolar exudates and inflammatory cell infiltration were obvious; pulmonary interstitium exhibited significant hyperemia and severe hemorrhage.…”

“…PV, SVC, IVC, and hepatic artery were all unclamped. The anhepatic phase lasted for 20 ± 1 min on average [ 5 , 9 , 14 ].…”

“…During liver transplantation, because inferior vena cava and the portal vein are interrupted, intestinal congestion becomes obvious, which results in intestine motility and barriers destroyed significantly. Both bacterial translocation and enterogenous endotoxin are over-produced, leading to susceptible organs injuries, including lungs [ 5 , 6 ]. As reported, ALI contributed to mortality of patients suffering from liver transplantation, because patients with ALI prone to develop acute respiratory distress syndrome (ARDS), mortality rate among of which could be as high as 76.5 % [ 6 , 7 ].…”

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

“…Our present work reveals that in lungs from rats with OALT, Serpin protease 5 inhibitor B1 (SERPINB1), was upregulated with concomitantly increase of STAT3 and HO-1 protein expression. We further demonstrated that administration of SERPINB1 reduced inflammation and oxidative stress in the lungs after OALT that was associated with enhanced STAT3 and HO-1, which collectively attenuated ALI in OALT.…”

“…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.…”