Oral administration of oleuropein attenuates cisplatin-induced acute renal injury in mice. - GreenMedInfo Summary
Oral administration of oleuropein attenuates cisplatin-induced acute renal injury in mice through inhibition of ERK signaling.
Mol Nutr Food Res. 2015 Nov 25. Epub 2015 Nov 25. PMID: 26603374
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 two 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 resultedin 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 antioxidantmarkers.
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. This article is protected by copyright. All rights reserved.