Protocatechuic Aldehyde Attenuates Cisplatin-Induced Acute Kidney Injury by Suppressing Nox-Mediated Oxidative Stress and Renal Inflammation.
Protocatechuic Aldehyde Attenuates Cisplatin-Induced Acute Kidney Injury by Suppressing Nox-Mediated Oxidative Stress and Renal Inflammation.
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原儿茶醛通过抑制 Nox 介导的氧化应激和肾脏炎症来减轻顺铂引起的急性肾损伤。
DOI：
10.3389/fphar.2016.00479
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发表时间：
2016
影响因子：
5.6
通讯作者：
Meng XM
中科院分区：
文献类型：
--
作者：
Gao L;Wu WF;Dong L;Ren GL;Li HD;Yang Q;Li XF;Xu T;Li Z;Wu BM;Ma TT;Huang C;Huang Y;Zhang L;Lv X;Li J;Meng XM
顺铂是一种经典的化疗药物，广泛用于治疗不同类型的癌症，包括卵巢癌、头颈癌、睾丸癌和宫颈癌。然而，顺铂通过直接引发过度的炎症反应、氧化应激和肾小管上皮细胞的程序性死亡而导致急性肾损伤，所有这些都导致患者的高死亡率。在本研究中，我们检测了原儿茶醛(PA)在体外对顺铂处理的肾小管上皮细胞的保护作用，以及在体内对顺铂肾病的保护作用。PA是从丹参属植物丹参中分离得到的一种中药单体。结果表明，PA可以预防顺铂所致的肾功能下降和组织学损伤，这一点在mRNA和蛋白水平上都得到了证实。此外，PA通过抑制顺铂引起的氧化应激和程序性细胞死亡来减轻肾脏炎症，这一点在体外数据中得到了进一步的证实。值得注意的是，PA以剂量依赖的方式抑制NAPDH氧化酶，包括NOX2和NOX4。此外，沉默NOX4，而不是NOX2，可消除PA对顺铂诱导的肾损伤的抑制作用，提示NOX4可能在PA对顺铂诱导的急性肾损伤的保护作用中起关键作用。总而言之，我们的数据表明，PA通过抑制NOx介导的氧化应激和肾脏炎症而阻止顺铂诱导的急性肾损伤，而不损害顺铂的抗肿瘤活性。这些发现表明，PA及其衍生物可能成为接受顺铂治疗的癌症患者的潜在保护剂。
Cisplatin is a classic chemotherapeutic agent widely used to treat different types of cancers including ovarian, head and neck, testicular and uterine cervical carcinomas. However, cisplatin induces acute kidney injury by directly triggering an excessive inflammatory response, oxidative stress, and programmed cell death of renal tubular epithelial cells, all of which lead to high mortality rates in patients. In this study, we examined the protective effect of protocatechuic aldehyde (PA) in vitro in cisplatin-treated tubular epithelial cells and in vivo in cisplatin nephropathy. PA is a monomer of Traditional Chinese Medicine isolated from the root of S. miltiorrhiza (Lamiaceae). Results show that PA prevented cisplatin-induced decline of renal function and histological damage, which was confirmed by attenuation of KIM1 in both mRNA and protein levels. Moreover, PA reduced renal inflammation by suppressing oxidative stress and programmed cell death in response to cisplatin, which was further evidenced by in vitro data. Of note, PA suppressed NAPDH oxidases, including Nox2 and Nox4, in a dosage-dependent manner. Moreover, silencing Nox4, but not Nox2, removed the inhibitory effect of PA on cisplatin-induced renal injury, indicating that Nox4 may play a pivotal role in mediating the protective effect of PA in cisplatin-induced acute kidney injury. Collectively, our data indicate that PA blocks cisplatin-induced acute kidney injury by suppressing Nox-mediated oxidative stress and renal inflammation without compromising anti-tumor activity of cisplatin. These findings suggest that PA and its derivatives may serve as potential protective agents for cancer patients receiving cisplatin treatment.
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影响因子：
4.6
作者：
Sancho-Martínez SM;López-Novoa JM;López-Hernández FJ
通讯作者：
López-Hernández FJ
影响因子：
64.8
作者：
Scaffidi, P;Misteli, T;Bianchi, ME
通讯作者：
Bianchi, ME
DOI：
10.1016/j.bbrc.2012.11.018
发表时间：
2013-01-04
影响因子：
3.1
作者：
Jeong, Jin Boo;Lee, Seong-Ho
通讯作者：
Lee, Seong-Ho
肾小管坏死性凋亡在顺铂诱发的 AKI 中的作用
影响因子：
13.6
作者：
Xu, Yanfang;Ma, Huabin;Han, Jiahuai
通讯作者：
Han, Jiahuai
影响因子：
4.5
作者：
Domitrovic, Robert;Cvijanovic, Olga;Skoda, Marko
通讯作者：
Skoda, Marko