Protection of resveratrol on acute kidney injury in septic rats

Hum Exp Toxicol. 2017 Oct;36(10):1015-1022. doi: 10.1177/0960327116678298. Epub 2016 Nov 12.

Abstract

Aim: The aim of the study is to investigate protective effect of resveratrol (Res) on acute kidney injury (AKI) in sepsis.

Methods: Rats in sham group received sham operation; in sham + Res received sham operation and Res (3 mg/kg); in cecal ligation and puncture (CLP) established as sepsis; in CLP + Res (3 mg/kg) with sepsis and Res (3 mg/kg); and in CLP + Res (10 mg/kg) with sepsis and Res (10 mg/kg). Survival rate, serum indexes, inflammatory factors, NF-κB-P65, and SIRT1 were detected. Lipopolysaccharide (LPS) mesangial cell was with Res and SIRT1 silencing.

Results: (1) Res intervention improved survival rate of CLP rat. (2) Compared to sham, serum creatinine, blood urine nitrogen, serum cystatin C, neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, tumor necrosis factor-α, interleukin-1β, IL-6, and renal injury index increased in CLP group, while decreased in CLP + Res (3 mg/kg) and CLP + Res (10 mg/kg), significantly, as dose-dependent ( p < 0.05). (3) With Res, NF-κB-P65 and de-acetylated SIRT1 decreased, while SIRT1 and de-acetylated Nuclear factor kB-p65 9 NF-κB-P65) increased, significantly ( p < 0.05). (4) SIRT1 and de-acetylated NF-κB-P65 decreased in LPS cells, while SIRT1 increased after Res intervention, significantly ( p < 0.05). After silencing SIRT1, de-acetylated NF-κB-P65 increased, significantly ( p < 0.05).

Conclusions: Res increases the survival rate of septic rats by inhibiting inflammatory factors to ease AKI and promotes NF-κB-P65 de-acetylation by upregulating SIRT1.

Keywords: NF-κB-P65; Resveratrol; SIRT1; acute kidney injury; sepsis.

MeSH terms

  • Acute Kidney Injury / metabolism
  • Acute Kidney Injury / pathology
  • Acute Kidney Injury / physiopathology
  • Acute Kidney Injury / prevention & control*
  • Animals
  • Cytokines / blood
  • Glomerular Filtration Rate / drug effects
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney / pathology
  • Kidney / physiology
  • Male
  • Protective Agents / pharmacology
  • Protective Agents / therapeutic use*
  • Rats, Sprague-Dawley
  • Renal Circulation / drug effects
  • Resveratrol
  • Sepsis / drug therapy*
  • Sepsis / metabolism
  • Sepsis / pathology
  • Sepsis / physiopathology
  • Sirtuin 1 / metabolism
  • Stilbenes / pharmacology
  • Stilbenes / therapeutic use*
  • Transcription Factor RelA / metabolism

Substances

  • Cytokines
  • Protective Agents
  • Stilbenes
  • Transcription Factor RelA
  • Sirt1 protein, rat
  • Sirtuin 1
  • Resveratrol