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Oleuropein ameliorates cisplatin-induced oxidative damage, inflammation and apoptosis in mice kidneys by modulating CYP2E1, NF-κB and ERK1/2 expression

Oleuropein, a phenolic compound isolated from the leaves and fruit of the olive tree (Olea europea L.), has been shown to possess numerous pharmacological activities. The aim of the current study was to investigate the renoprotective effects of oleuropein against cisplatin (CP)-induced kidney injury. Male BALB/cN mice were gavaged daily 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. Oxidative stress in the kidneys was evidenced by overexpression 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, tumor necrosis factor-alpha (TNF-α) and cyclooxygenase-2 (COX-2) in the kidneys increased upon CP treatment, suggesting renal inflammation. CP intoxication increased expression of p53, Bax and active caspase-3, indicating apoptotic cell death, which was further confirmed by the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. CP administration resulted in enhanced phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2), involved in CP-induced renal cell apoptosis, but not c-Jun N-terminal kinases 1 and 2 (JNK1/2) and p38 mitogen activated protein kinase (MAPK). All these effects were dose-dependently diminished by oleuropein treatment. The results of the current study suggest that oleuropein attenuates CP-induced oxidative stress, inflammation and apoptosis at least in part through the suppression of CYP2E1 and NF-κB overexpression and the reduction of ERK1/2 phosphorylation.

oleuropein; cisplatin; oxidative stress; inflammation; apoptosis; MAPK

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