Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Sci Rep. 2018 May 9;8(1):7333. doi: 10.1038/s41598-018-25610-6.
Cisplatin is a commonly used chemotherapeutic agent in the treatment of different types of malignant tumors, but nephrotoxicity limits its usage. Therefore, in this study, we aimed to determine the possible protective effect of Huaiqihuang (HQH) extractum, a kind of Chinese herbal complex that consists of Trametes robiniophila Murr., Lycium barbarum and Polygonatum sibiricum, against nephrotoxicity induced by cisplatin in mice. We found that pretreatment with HQH significantly attenuated the cisplatin-induced increase in blood urea nitrogen (BUN), interstitial congestion, acute renal tubular injury and tubular cell apoptosis and necroptosis. It was further shown that HQH administration reduced cisplatin-induced release and nuclear-cytoplasmic translocation of HMGB1 and inactivated its downstream signaling molecules, TLR4 and NFκB, in renal tubular cells; as a result, HQH repressed cisplatin-induced TNF-α production. As dexamethasone (Dex) exerts renoprotective effects in severe Acute kidney injury (AKI), we compared it with HQH and found that HQH showed similar renoprotective effects to dexamethasone via similar mechanisms. Considering the potential side effects of corticosteroids, reducing the effectiveness of treatment and shortening survival in solid tumor patients, we suggest administration of HQH as a potential adjuvant for cisplatin therapy in solid tumor patients to preserve renal function.
顺铂是一种常用于治疗不同类型恶性肿瘤的化疗药物,但肾毒性限制了其应用。因此,本研究旨在探讨槐芪黄提取物(HQH)对顺铂诱导的小鼠肾毒性的可能保护作用。槐芪黄提取物由槐耳、枸杞和黄精组成,是一种中药复方。我们发现,HQH 预处理可显著减轻顺铂诱导的血尿素氮(BUN)升高、间质充血、急性肾小管损伤和肾小管细胞凋亡和坏死。进一步研究表明,HQH 可减少顺铂诱导的 HMGB1 的释放和核质易位,并使 HMGB1 的下游信号分子 TLR4 和 NFκB 失活,从而抑制顺铂诱导的 TNF-α的产生。由于地塞米松(Dex)在严重急性肾损伤(AKI)中具有肾脏保护作用,我们将其与 HQH 进行了比较,发现 HQH 通过类似的机制发挥与地塞米松相似的肾脏保护作用。考虑到皮质类固醇的潜在副作用,会降低治疗效果并缩短实体瘤患者的生存期,我们建议将 HQH 作为顺铂治疗实体瘤患者的辅助药物,以保护肾功能。