Abstract

Anticancer drug like Cisplatin are associated with serious problem like nephrotoxicity. The effect of Kaempferol is a plant-derived flavonoid compound. The present work evaluated the effect of Kaempferol in mouse model of Cisplatin mediated nephrotoxicity also the involved mechanism. Oxidative stress, kidney function, histology, inflammation, apoptosis, level of proteins, Nrf2 translocation and its effect on cascades such as NF-κB and ERK were studied. It was observed that the pre-treatment of KPF reduced the Cisplatin mediated oxidative stress, inflammation, apoptosis and ameliorated renal injury and its functioning. Kaempferol suppressed the Cisplatin induced infiltration of mononuclear cells, levels of TNF-α, iNOS, IL-12, activation of NF-κB, phosphorylation of IκBα and nuclear translocation of p65 in renal tissues. Also KPF attenuated Cisplatin mediated phosphorylation of p38, ERK1/2 and JNK in renal tissues. KPF also corrected the levels of renal antioxidants and elevated the nuclear levels of HO-1 and Nrf2 in renal tissues. KPF attenuated the Cisplatin mediated apoptosis via down-regulating the levels of TP53, Bax/Bcl2 imbalance, activating caspase-3/9 and PARP. The outcomes conclude that KPF ameliorates Cisplatin-mediated nephrotoxicity by modulating oxidative stress, inflammation and apoptosis via ERK and NF-κB pathway.

中文翻译：

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山奈酚通过通过ERK和NF-κB途径调节氧化应激，炎症和细胞凋亡来改善顺铂诱导的肾毒性

摘要

像顺铂这样的抗癌药物会引起严重的问题，例如肾毒性。山emp酚的作用是植物来源的类黄酮化合物。目前的工作评估了Kaempferol在顺铂介导的肾毒性小鼠模型中的作用，也涉及了其参与的机制。研究了氧化应激，肾脏功能，组织学，炎症，凋亡，蛋白质水平，Nrf2易位及其对级联反应如NF-κB和ERK的影响。观察到KPF的预处理减少了顺铂介导的氧化应激，炎症，细胞凋亡和改善的肾损伤及其功能。山萘酚抑制了顺铂诱导的单核细胞浸润，TNF-α，iNOS，IL-12的水平，NF-κB的活化，IκBα的磷酸化和p65在肾组织中的核易位。KPF还减弱了顺铂介导的肾组织中p38，ERK1 / 2和JNK的磷酸化。KPF还纠正了肾脏抗氧化剂的水平，并提高了肾组织中HO-1和Nrf2的核水平。KPF通过下调TP53，Bax / Bcl2失衡，激活caspase-3 / 9和PARP的水平来减弱顺铂介导的细胞凋亡。结果表明，KPF通过ERK和NF-κB途径调节氧化应激，炎症和细胞凋亡，从而改善了顺铂介导的肾毒性。