Wang Zhu, Sun Wansen, Sun Xi, Wang Ye, Zhou Meilan
Department of Traditional Chinese Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University (Xibei Hospital), Xi'an, 710004, Shaanxi, China.
Department of Nephropathy, Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine, Xianyang, 712000, Shaanxi, China.
AMB Express. 2020 Mar 26;10(1):58. doi: 10.1186/s13568-020-00993-w.
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.
像顺铂这样的抗癌药物会引发诸如肾毒性等严重问题。山柰酚是一种植物源黄酮类化合物。本研究评估了山柰酚在顺铂介导的肾毒性小鼠模型中的作用及其相关机制。研究了氧化应激、肾功能、组织学、炎症、细胞凋亡、蛋白质水平、Nrf2易位及其对NF-κB和ERK等信号通路的影响。结果发现，山柰酚预处理可减轻顺铂介导的氧化应激、炎症和细胞凋亡，改善肾损伤及其功能。山柰酚抑制了顺铂诱导的肾组织中单核细胞浸润、TNF-α、iNOS、IL-12水平，NF-κB激活、IκBα磷酸化和p65核转位。此外，山柰酚减弱了顺铂介导的肾组织中p38、ERK1/2和JNK的磷酸化。山柰酚还纠正了肾组织中抗氧化剂水平，提高了肾组织中HO-1和Nrf2的核水平。山柰酚通过下调TP53水平、Bax/Bcl2失衡、激活caspase-3/9和PARP来减轻顺铂介导的细胞凋亡。研究结果表明，山柰酚通过ERK和NF-κB途径调节氧化应激、炎症和细胞凋亡，从而改善顺铂介导的肾毒性。
