Bisdemethoxycurcumin attenuates cisplatin-induced renal injury through anti-apoptosis, anti-oxidant and anti-inflammatory
Bisdemethoxycurcumin attenuates cisplatin-induced renal injury through anti-apoptosis, anti-oxidant and anti-inflammatory
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DOI：
10.1016/j.ejphar.2020.173026
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发表时间：
2020-05-05
影响因子：
5
通讯作者：
He, Qiaojun
中科院分区：
文献类型：
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作者：
Jin, Fuquan;Chen, Xueqin;He, Qiaojun
顺铂是一种广泛使用的化疗药物，是多种肿瘤的一线治疗药物。不幸的是，其对多种正常组织和器官的不良影响，尤其是肾毒性，威胁着患者的生命。尽管顺铂肾毒性的机制已被证实与氧化应激、肾小管上皮细胞凋亡和炎症反应有关，但临床上尚无有效的预防策略。在此，我们发现天然化合物双去甲氧基姜黄素（BDMC）在5-20μM浓度下可在体外显着减弱顺铂诱导的肾小管上皮细胞凋亡，并且在50mg/kg剂量下对顺铂诱导的小鼠肾损伤具有显着的保护作用。从机制上讲，BDMC 通过抑制顺铂诱导的 p53 上调来减弱顺铂诱导的肾小管上皮细胞凋亡。同时，BDMC 通过抑制顺铂诱导的核因子红细胞 2 相关因子 2 (Nrf2) 的下调来抵消氧化应激。 BDMC 还显着降低细胞间粘附分子 1 (ICAM-1) 和单核细胞趋化蛋白 1 (MCP-1) 蛋白的表达，以及核因子 kappa B (NF-kappa B p65) 的 p65 亚基的表达和易位到细胞核中，所有这些在顺铂治疗下均在肾脏中增加。总的来说，BDMC可能是一种有效的预防顺铂引起的肾毒性的策略，我们的研究可能为药物毒性的治疗提供新的思路。
Cisplatin is a widely used chemotherapy drug that is first-line therapy for a variety of tumors. Unfortunately, its adverse effects on various normal tissues and organs, especially nephrotoxicity, threaten the life of patients. Although the mechanism of cisplatin nephrotoxicity has been confirmed to be related to oxidative stress, apoptosis of renal tubular epithelial cells and inflammatory response, there is no effective prevention strategy in the clinic. Here, we found that bisdemethoxycurcumin (BDMC), a natural compound, can significantly attenuates cisplatin-induced apoptosis of renal tubular epithelial cells in vitro at the concentration of 5-20 mu M and has a significant protective effect on cisplatin-induced kidney injury in mice at the dose of 50 mg/kg. Mechanistically, BDMC attenuates cisplatin-induced apoptosis of renal tubular epithelial cells by inhibiting cisplatin-induced upregulation of p53. Meanwhile, BDMC counteracts oxidative stress by inhibiting cisplatin-induced down-regulation of nuclear factor erythroid-2-related factor 2 (Nrf2). BDMC also significantly reduced the expression of intercellular adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1) proteins, as well as the expression and translocation of the p65 subunit of nuclear factor-kappa B (NF-kappa B p65) into the nucleus, all of which were increased in the kidney by cisplatin treatment. Collectively, BDMC might be an effective prevention strategy which could against cisplatin-induced nephrotoxicity, and our research may shed a new light on treatment of drug toxicity.