Oral administration of oleuropein attenuates cisplatin-induced acute renal injury in mice through inhibition of ERK signaling

Mol Nutr Food Res. 2016 Mar;60(3):530-41. doi: 10.1002/mnfr.201500409. Epub 2015 Dec 18.

Abstract

Scope: Oleuropein possesses numerous health beneficial effects. We investigated the renoprotective effects of oleuropein against cisplatin (CP) induced kidney injury.

Methods and results: Male BALB/cN mice were orally gavaged with 5, 10 and 20 mg oleuropein/kg body weight for 2 days, 48 h after intraperitoneal injection of CP (13 mg/kg). Four days after CP administration, serum creatinine and blood urea nitrogen (BUN) levels were significantly elevated, with histopathological changes in renal tissue. In addition, renal oxidative stress was evidenced by increased expression of 3-nitrotyrosine (3-NT), 4-hydroxynonenal (4-HNE), cytochrome P450 E1 (CYP2E1) and heme oxygenase-1 (HO-1). The expression of nuclear factor-kappaB (NF-κB) p65, phospho-p65, tumor necrosis factor-alpha (TNF-α) and cyclooxygenase-2 (COX-2) in the kidneys increased upon CP treatment, suggesting renal inflammation. CP intoxication increased the expression of p53, Bax and caspase-3 and induced apoptosis in the kidneys. CP administration also resulted in enhanced phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2). All these effects were dose dependently diminished by oleuropein. Oral administration of PD0325901, an MEK inhibitor, coincided with the oleuropein-mediated suppression of apoptotic, inflammatory and antioxidant markers.

Conclusion: The results of the current study suggest that oleuropein attenuated CP-induced acute renal injury, which was mediated through the inhibition of ERK signaling.

Keywords: Apoptosis; Cisplatin nephrotoxicity; Inflammation; MAPK; Oleuropein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / chemically induced
  • Acute Kidney Injury / metabolism
  • Acute Kidney Injury / prevention & control*
  • Administration, Oral
  • Animals
  • Antineoplastic Agents / adverse effects
  • Apoptosis / drug effects
  • Cisplatin / adverse effects*
  • Enzyme Inhibitors / pharmacology
  • Iridoid Glucosides
  • Iridoids / administration & dosage
  • Iridoids / pharmacology*
  • Kidney / drug effects
  • Kidney / metabolism
  • Kidney / pathology
  • MAP Kinase Signaling System / drug effects*
  • Male
  • Mice, Inbred BALB C
  • Nephritis / chemically induced
  • Nephritis / drug therapy
  • Nephritis / metabolism
  • Oxidative Stress / drug effects
  • Protective Agents / pharmacology*

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Iridoid Glucosides
  • Iridoids
  • Protective Agents
  • oleuropein
  • Cisplatin