Effect of oleuropein on oxidative stress, inflammation and apoptosis induced by ischemia-reperfusion injury in rat kidney

Life Sci. 2020 Aug 15:255:117833. doi: 10.1016/j.lfs.2020.117833. Epub 2020 May 22.


Aims: This study aimed to evaluate the effect of oleuropein (OLE), the main phenolic compound present in olive leaves, on kidney ischemia-reperfusion injury (IRI) and to explore the underlying protective mechanism.

Main methods: Rat kidneys were subjected to 60 min of bilateral warm ischemia followed by 120 min of reperfusion. OLE was administered orally 48 h, 24 h and 30 min prior to ischemia at doses of 10, 50 and 100 mg/kg body weight. The creatinine, urea, uric acid concentrations and lactate dehydrogenase (LDH) activity in plasma were evaluated. Oxidative stress and inflammation parameters were also assessed. Renal expression of AMP-activated protein kinase (p-AMPK), endothelial nitric oxide synthase (eNOS), mitogen-activated protein kinases (MAPK), inflammatory proteins and apoptotic proteins were evaluated using Western blot.

Key findings: Our results showed that OLE at 50 mg/kg reduced kidney IRI as revealed by a significant decrease of plasmatic creatinine, urea, uric acid concentrations and LDH activity. In parallel, OLE up-regulated antioxidant capacities. Moreover, OLE diminished the level of CRP and the expression of cyclooxygenase 2 (COX-2). Finally, OLE enhanced AMPK phosphorylation as well as eNOS expression whereas MAPK, and cleaved caspase-3 implicated in cellular apoptosis were attenuated in the ischemic kidneys.

Significance: In conclusion, this study shows that OLE could be used as therapeutic agent to reduce IRI through its anti-oxidative, anti-inflammatory and anti-apoptotic properties.

Keywords: Apoptosis; Inflammation; Ischemia; Kidney; Oleuropein; Oxidative stress.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / pharmacology
  • Antioxidants / administration & dosage
  • Antioxidants / pharmacology
  • Apoptosis / drug effects
  • Dose-Response Relationship, Drug
  • Inflammation / prevention & control*
  • Iridoid Glucosides
  • Iridoids / administration & dosage
  • Iridoids / pharmacology*
  • Kidney / drug effects*
  • Kidney / pathology
  • Male
  • Oxidative Stress / drug effects*
  • Rats
  • Rats, Wistar
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / physiopathology
  • Time Factors


  • Anti-Inflammatory Agents
  • Antioxidants
  • Iridoid Glucosides
  • Iridoids
  • oleuropein