title: Oral administration of oleuropein attenuates cisplatin-induced acute renal injury in mice through inhibition of ERK signaling.
abstract: METHODS
  Oleuropein possesses numerous health beneficial effects. We investigated the renoprotective effects of oleuropein against cisplatin (CP) induced kidney injury.
  
  
  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.
  
  
  CONCLUSIONS
  The results of the current study suggest that oleuropein attenuated CP-induced acute renal injury, which was mediated through the inhibition of ERK signaling.
authors.affiliation: Department of Chemistry and Biochemistry, Medical Faculty, University of Rijeka, Rijeka, Croatia.
authors.forename: Iva
authors.initials: I
authors.lastname: Potočnjak
authors.affiliation: Department of Physiology and Immunology, Medical Faculty, University of Rijeka, Rijeka, Croatia.
authors.forename: Marko
authors.initials: M
authors.lastname: Škoda
authors.affiliation: Department of Histology and Embriology, Medical Faculty, University of Rijeka, Rijeka, Croatia.
authors.forename: Ester
authors.initials: E
authors.lastname: Pernjak-Pugel
authors.affiliation: Department of Nephrology and Dialysis, University of Rijeka, University Hospital Rijeka, Rijeka, Croatia.
authors.forename: Martina Pavletić
authors.initials: MP
authors.lastname: Peršić
authors.affiliation: Department of Chemistry and Biochemistry, Medical Faculty, University of Rijeka, Rijeka, Croatia.
authors.forename: Robert
authors.initials: R
authors.lastname: Domitrović
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects; D017209:Apoptosis / Q000187:drug effects; D002945:Cisplatin / Q000009:adverse effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D057888:Iridoid Glucosides; D039823:Iridoids / Q000008:administration & dosage / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D008807:Mice, Inbred BALB C; D009393:Nephritis / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D057888:Iridoid Glucosides; D039823:Iridoids; D020011:Protective Agents; C002769:oleuropein; D002945:Cisplatin
keywords: Apoptosis; Cisplatin nephrotoxicity; Inflammation; MAPK; Oleuropein