期刊
TOXICOLOGY
卷 310, 期 -, 页码 115-123出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.tox.2013.05.015
关键词
Cisplatin nephrotoxicity; Luteolin; Oxidative/nitrosative stress; Inflammation; Apoptosis
资金
- Ministry of Science, Education and Sport, Republic of Croatia [062-0000000-3554]
The aim of this study was to investigate the effects of flavone luteolin against cisplatin (CP)-induced kidney injury in mice. Luteolin at doses of 10 mg/kg was administered intraperitoneally (ip) once daily for 3 days following single CP (10 or 20 mg/kg) ip injection. Mice were sacrificed 24 h after the last dose of luteolin. The CP treatment significantly increased serum creatinine and blood urea nitrogen and induced pathohistological changes in the kidneys. Renal oxidative/nitrosative stress was evidenced by decreased glutathione (GSH) levels and increased 3-nitrotyrosine (3-NT) and 4-hydroxynonenal (4-HNE) formation as well as cytochrome P450 2E1 (CYP2E1) expression. The CP administration triggered inflammatory response in mice kidneys through activation of nuclear factor-kappaB (NE-kappa B) and overexpression of tumor necrosis factor-alpha (THE-et) and cyclooxygenase-2 (COX-2). Simultaneously, the increase in renal p53 and caspase-3 expression indicated apoptosis of tubular cells. The administration of luteolin significantly reduced histological and biochemical changes induced by CP, decreased platinum (Pt) levels and suppressed oxidative/nitrosative stress, inflammation and apoptosis in the kidneys. These results suggest that luteolin is an effective nephroprotective agent, with potential to reduce Pt accumulation in the kidneys and ameliorate CP-induced nephrotoxicity. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
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