Anti-apoptotic and anti-inflammatory effects of naringin on cisplatin-induced renal injury in the rat
Anti-apoptotic and anti-inflammatory effects of naringin on cisplatin-induced renal injury in the rat
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DOI：
10.1016/j.cbi.2015.11.019
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发表时间：
2016-01-05
影响因子：
5.1
通讯作者：
Fetoui, Hamadi
中科院分区：
文献类型：
--
作者：
Chtourou, Yassine;Aouey, Baktha;Fetoui, Hamadi
肾毒性是顺铂化疗的常见并发症，限制了顺铂的临床应用。柚皮苷是一种天然黄酮类化合物，在炎症和细胞凋亡中发挥重要作用，但其在顺铂肾毒性中的作用尚不清楚。在这项研究中，我们首先评估了ROS过度产生和炎症在老年大鼠顺铂诱导的肾毒性中的作用，然后我们研究了柚皮苷（20，50或100 mg/kg体重）治疗后肾功能，组织学损伤，炎症反应和肾组织细胞凋亡的变化。顺铂导致肾脏标志物、脂质过氧化、蛋白质和DNA氧化以及ROS形成增加。肾肿瘤坏死因子-α（TNF-α）和亚硝酸盐水平也升高。与正常对照组相比，顺铂组大鼠肾组织核因子-κ B（NF-κ B）、诱导型一氧化氮合酶（iNOS）、caspase-3和p53表达上调。顺铂组也出现组织学改变。以不同剂量（25，50和100 mg/kg）给予柚皮苷能够防止肾功能恶化，消除抗氧化酶活性的下降，并抑制TBARS，亚硝酸盐和TNF-α浓度的增加。结论：氧化应激和炎症反应在顺铂肾毒性中起重要作用，柚苷可能成为治疗顺铂肾毒性的有效药物。(C)2015爱思唯尔爱尔兰有限公司版权所有。
Nephrotoxicity is a common complication of cisplatin chemotherapy and thus limits the use of cisplatin in clinic. Naringin, a natural flavonoid, plays important roles in inflammation and apoptosis in some inflammatory diseases; however, its roles in cisplatin-induced nephrotoxicity remain unclear. In this study, we first assessed the involvement of ROS overproduction and inflammation in cisplatin-induced nephrotoxicity in aged rats, and then we investigated the changes of renal function, histological injury, inflammatory response, and apoptosis in renal tissues after treatment with naringin (20, 50 or 100 mg/kg body weight). Cisplatin resulted in an increase of renal markers, lipid peroxidation, protein and DNA oxidation, and ROS formation. Renal tumor necrosis factor-alpha (TNF-alpha) and nitrite levels were also elevated. Expressions of nuclear factor-kappa B (NF-kappa B), inductible nitric oxide synthase (iNOS), caspase-3 and p53 were up-regulated in renal tissues of Cis-treated rats compared with the normal control group. Histopathological changes were also observed in cisplatin group. Adminstration of naringin at different doses (25, 50 and 100 mg/kg) was able to protect against the deterioration in kidney function, abrogate the decline in antioxidant enzyme activities and suppressed the increase in TBARS, nitrite and TNF-alpha concentrations. Moreover, naringin inhibited NF-kappa B and iNOS pathways, caspase-3 and p53 activation and improved the histological changes induced by cisplatin.In conclusion, our studies suggest that oxidative stress and inflammation might play important roles in the development of cisplatin-induced nephrotoxicity and naringin might become an effective therapeutic strategy for this disease. (C) 2015 Elsevier Ireland Ltd. All rights reserved.