Propofol Reduces Renal Ischemia Reperfusion-mediated Necroptosis by Up-regulation of SIRT1 in Rats

Inflammation. 2022 Oct;45(5):2038-2051. doi: 10.1007/s10753-022-01673-6. Epub 2022 Apr 23.

Abstract

Propofol (Pro) is well known to regulate the asleep-awake-asleep technique. Increasing indication recommends that Pro also has promising properties such as anti-oxidant and anti-inflammation belongings in several disease models. It has been described that Pro has beneficial properties against renal ischemia/reperfusion (rI/R)-mediated acute lung injury (ALI). Nevertheless, pathogenesis underlying the beneficial action of Pro on the remote ALI mediated by rI/R remains unwell unstated. In this research, we displayed that Pro administration remarkably inhibits rI/R-mediated pro-inflammatory cytokines production. Increased levels of oxidative stress were mainly decreased by Pro. Pro administration ameliorated apoptosis-related caspase-3 activation. Furthermore, the levels of crucial necroptosis-associated protein were reduced by Pro. Sirtuin 1 (SIRT1) inhibitor attenuated the aforementioned changes of Pro. In conclusion, these results propose that Pro attenuates rI/R-induced inflammation, oxidative stress, apoptosis, and necroptosis by up-regulation of SIRT1 in rats. Our findings disclose an original pathogenesis underlying the beneficial effect of Pro against rI/R-mediated ALI and reinforce the knowledge that Pro might be a hopeful beneficial agent for the rI/R-mediated ALI.

Keywords: Acute kidney injury; Acute lung injury; Alveolar macrophages; Apoptosis; Inflammation; Necroptosis; Oxidative stress.; Propofol; Renal ischemia–reperfusion; SIRT1.

MeSH terms

  • Acute Lung Injury* / etiology
  • Animals
  • Antioxidants / pharmacology
  • Apoptosis
  • Caspase 3 / metabolism
  • Cytokines / metabolism
  • Ischemia / complications
  • Ischemia / pathology
  • Kidney Diseases* / complications
  • Necroptosis
  • Oxidative Stress
  • Propofol* / pharmacology
  • Propofol* / therapeutic use
  • Rats
  • Reperfusion / adverse effects
  • Reperfusion Injury* / complications
  • Reperfusion Injury* / drug therapy
  • Reperfusion Injury* / prevention & control
  • Sirtuin 1 / metabolism
  • Up-Regulation

Substances

  • Antioxidants
  • Cytokines
  • Caspase 3
  • Sirt1 protein, rat
  • Sirtuin 1
  • Propofol