Protective role of naringin against cisplatin induced oxidative stress, inflammatory response and apoptosis in rat striatum via suppressing ROS-mediated NF-κB and P53 signaling pathways
Protective role of naringin against cisplatin induced oxidative stress, inflammatory response and apoptosis in rat striatum via suppressing ROS-mediated NF-κB and P53 signaling pathways
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DOI：
10.1016/j.cbi.2015.06.036
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发表时间：
2015-09-05
影响因子：
5.1
通讯作者：
Fetoui, Hamadi
中科院分区：
文献类型：
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作者：
Chtourou, Yassine;Aouey, Bakhta;Fetoui, Hamadi
顺铂（Cisplatin，Cis）是一种有效的化疗药物，已成功用于治疗多种恶性肿瘤，但由于其剂量依赖性毒性，其使用受到限制。本研究旨在探讨柚皮苷（一种普遍存在的黄酮类化合物）对顺式肾上腺素诱导的老龄大鼠纹状体损伤的保护作用。简言之，将实验程序分为两组实验。首先将动物分为4组：对照组、Nar 25 mg/kg组、Nar 50 mg/kg组和Nar 100 mg/kg组。第二组动物分为4组：Cis（5 mg/kg/周，连续5周）、Cis + Nar（25 mg/kg）、Cis + Nar（50 mg/kg）和Cis + Nar（100 mg/kg）。Cis给药（5 mg/kg/周，连续5周）导致还原型谷胱甘肽和抗坏血酸浓度下降。膜结合ATP酶和谷胱甘肽过氧化物酶（GPx）活性降低，过氧化氢酶（CAT）和超氧化物歧化酶（SOD）活性升高。此外，在纹状体组织中，Cis显著增强P53、核因子κ B通路（NF κ B）和肿瘤坏死因子（TNF-α）的mRNA基因表达。Cis组出现明显的氧化/亚硝化应激，表现为丙二醛（MDA）、蛋白质羰基（PCO）、活性氧（ROS）和亚硝酸盐（NO）浓度升高。柚苷（25、50和100 mg/kg）给药能够防止纹状体组织的恶化，消除抗氧化酶活性的变化，并抑制MDA、PCO、NO和TNF-α的增加。浓度的此外，Nar还能抑制P53、NF κ B B和TNF-α通路介导的炎症和凋亡，改善Cis诱导的组织学改变。因此，这些发现证明了Nar通过减弱促炎和凋亡介质并提高纹状体组织中的抗氧化能力而具有神经保护性质。结果表明，Nar对Cis诱导的老龄大鼠纹状体损伤有较好的保护作用，可作为治疗脑损伤的有效食品和保健品。出版社：Elsevier爱尔兰Ltd.
Cisplatin (Cis) is an effective chemotherapeutic agent successfully used in the treatment of a wide range of malignancies while its usage is limited due to its dose-dependent toxicity. The present study was conducted to investigate the efficacy of naringin, an ubiquitous flavonoid, against Cis-induced striatum injury in Wistar aged rats. Briefly, the experimental procedures were divided in two sets of experiments. In the first, the animals were divided into 4 groups: control, Nar 25 mg/kg, Nar 50 mg/kg and Nar 100 mg/kg. In the second, the animals were divided into 4 groups: Cis (5 mg/kg/week for 5 consecutive weeks), Cis + Nar (25 mg/kg), Cis + Nar (50 mg/kg) and Cis + Nar (100 mg/kg). The administration of Cis (5 mg/kg/week for 5 consecutive weeks) resulted in a decline in the concentrations of reduced glutathione and ascorbic acid. The activity of membrane bound ATPases and glutathione peroxidase (GPx) were decreased while the activity of catalase (CAT) and superoxide dismutase (SOD) were increased. Further, in striatum tissue, Cis significantly enhance the mRNA gene expression of P53, nuclear factor kappa B pathway (NF kappa B) and tumor necrosis factor (TNF-alpha). Oxidative/nitrosative stress was evident in Cis group by increased malondialdehyde (MDA), protein carbonyls (PCO), reactive oxygen species (ROS) and nitrite concentration (NO). Naringin (25, 50 and 100 mg/kg) administration was able to protect against deterioration in striatum tissue, abrogate the change in antioxidant enzyme activities and suppressed the increase in MDA, PCO, NO and TNF-alpha. concentrations. Moreover, Nar inhibited P53, NF kappa B and TNF-alpha pathways mediated inflammation and apoptosis, and improved the histological changes induced by Cis. Thus, these findings demonstrated the neuroprotective nature of Nar by attenuating the pro-inflammatory and apoptotic mediators and improving antioxidant competence in striatum tissue. These results imply that Nar has perfect effect against Cis-induced striatum injury in aged rats, which should be developed as an effective food and healthcare product for the treatment of brain injury in the future. Published by Elsevier Ireland Ltd.