Luteolin ameliorates cisplatin-induced nephrotoxicity in mice through inhibition of platinum accumulation, inflammation and apoptosis in the kidney
Luteolin ameliorates cisplatin-induced nephrotoxicity in mice through inhibition of platinum accumulation, inflammation and apoptosis in the kidney
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DOI：
10.1016/j.tox.2013.05.015
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发表时间：
2013-08-09
期刊：
影响因子：
4.5
通讯作者：
Skoda, Marko
中科院分区：
文献类型：
--
作者：
Domitrovic, Robert;Cvijanovic, Olga;Skoda, Marko
本研究旨在探讨黄酮木樨草素对顺铂（CP）所致小鼠肾损伤的保护作用。在单次CP（10或20 mg/kg）ip注射后，以10 mg/kg的剂量腹膜内（ip）施用木犀草素，每天一次，持续3天。在最后一剂毛地黄黄酮后24小时处死小鼠。CP治疗显著增加血清肌酐和血尿素氮，并诱导肾脏病理组织学变化。肾脏氧化/亚硝化应激表现为谷胱甘肽（GSH）水平降低、3-硝基酪氨酸（3-NT）和4-羟基壬烯醛（4-HNE）形成以及细胞色素P450 2 E1（CYP 2 E1）表达增加。CP给药通过激活核因子-κ B（NE-κ B）和过表达肿瘤坏死因子-α（THE-et）和环氧合酶-2（考克斯-2）引发小鼠肾脏中的炎症反应。同时，肾脏p53和caspase-3表达的增加表明肾小管细胞凋亡。毛地黄黄酮的管理显着减少CP诱导的组织学和生化变化，降低铂（Pt）水平和抑制氧化/亚硝化应激，炎症和细胞凋亡的肾脏。这些结果表明，毛地黄黄酮是一种有效的肾保护剂，有可能减少铂在肾脏中的积累，改善CP诱导的肾毒性。(C)2013爱思唯尔爱尔兰有限公司版权所有。
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.