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Oral administration of oleuropein attenuates cisplatin‐induced acute renal injury in mice through inhibition of ERK signaling
Author(s) -
Potočnjak Iva,
Škoda Marko,
PernjakPugel Ester,
Peršić Martina Pavletić,
Domitrović Robert
Publication year - 2016
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201500409
Subject(s) - oleuropein , pharmacology , mapk/erk pathway , kidney , chemistry , oxidative stress , intraperitoneal injection , oral administration , blood urea nitrogen , nitrotyrosine , antioxidant , endocrinology , medicine , kinase , biochemistry , nitric oxide , nitric oxide synthase
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.