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

Mol Med Rep. 2015 Mar;11(3):2348-54. doi: 10.3892/mmr.2014.2924. Epub 2014 Nov 11.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Lung Injury / drug therapy
  • Acute Lung Injury / etiology*
  • Acute Lung Injury / metabolism*
  • Acute Lung Injury / pathology
  • Animals
  • Disease Models, Animal
  • Hypnotics and Sedatives / pharmacology*
  • Liver Transplantation / adverse effects*
  • Male
  • NADPH Oxidases / metabolism*
  • Oxidative Stress / drug effects
  • Pneumonia / drug therapy
  • Pneumonia / etiology
  • Pneumonia / metabolism
  • Pneumonia / pathology
  • Propofol / pharmacology*
  • Protective Agents / pharmacology
  • Rats
  • Signal Transduction / drug effects*

Substances

  • Hypnotics and Sedatives
  • Protective Agents
  • NADPH Oxidases
  • Propofol