Rutin, a quercetin glycoside, alleviates acute endotoxemic kidney injury in C57BL/6 mice via suppression of inflammation and up-regulation of antioxidants and SIRT1

Eur J Pharmacol. 2018 Aug 15:833:307-313. doi: 10.1016/j.ejphar.2018.06.019. Epub 2018 Jun 18.

Abstract

Acute kidney injury (AKI) is a common complication following severe sepsis, its incidence is increasing, and it is associated with a high rate of morbidity and mortality. Rutin is a glycoside of the bioflavonoid quercetin with various protective effects due to its antioxidant and anti-inflammatory potential. In this research, we tried to assess the protective effect of rutin administration in a model of AKI in C57BL/6 mice. For induction of AKI, lipopolysaccharide (LPS) was injected once (10 mg/kg, i.p.) and rutin was p.o. given at doses of 50 or 200 mg/kg. Treatment of LPS-challenged group with rutin lowered serum level of creatinine and blood urea nitrogen (BUN), restored to some extent renal oxidative stress-related indices such as malondialdehyde (MDA), glutathione (GSH), and activity of superoxide dismutase (SOD) and catalase. In addition, rutin brought back renal nuclear factor-kappaB (NF-κB), toll-like receptor 4 (TLR4), cyclooxygenase-2 (COX2), sirtuin 1 (SIRT1), tumor necrosis factor α (TNFα), interleukin-6, and caspase 3 activity to their control levels. Moreover, protective effect of rutin was in accordance to a dose-dependent manner. Collectively, rutin is capable to mitigate LPS-induced AKI via appropriate modulation of renal oxidative stress, inflammation, and apoptosis.

Keywords: Acute kidney injury; Apoptosis; Inflammation; Lipopolysaccharide; Oxidative stress; Rutin.

MeSH terms

  • Acute Kidney Injury / drug therapy*
  • Acute Kidney Injury / etiology
  • Acute Kidney Injury / physiopathology
  • Animals
  • Antioxidants / pharmacology*
  • Antioxidants / therapeutic use
  • Apoptosis / drug effects
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Endotoxemia / chemically induced
  • Endotoxemia / complications
  • Escherichia coli
  • Female
  • Humans
  • Inflammation / drug therapy*
  • Inflammation / etiology
  • Kidney / drug effects
  • Kidney / physiopathology
  • Lipopolysaccharides / toxicity
  • Mice
  • Mice, Inbred C57BL
  • Oxidative Stress / drug effects
  • Rutin / pharmacology*
  • Rutin / therapeutic use
  • Sirtuin 1 / metabolism*
  • Up-Regulation

Substances

  • Antioxidants
  • Lipopolysaccharides
  • Rutin
  • Sirt1 protein, mouse
  • Sirtuin 1