Department of Clinical Pharmacology, Affiliated Hospital of Nanjing University of Chinese Medicine, No. 155 Hanzhong Road, Nanjing, 210029, China.
School of pharmacy, China Pharmaceutical University, No. 639 Longmian Road, Nanjing, 211198, China.
Sci Rep. 2017 Jun 15;7(1):3619. doi: 10.1038/s41598-017-03249-z.
The side effects of cisplatin (CDDP), notably nephrotoxicity, greatly limited its use in clinical chemotherapy. HuangQi Injections (HI), a commonly used preparation of the well-known Chinese herbal medicine Astragali radix, appeared to be promising treatment for nephrotoxicity without compromising the anti-tumor activity of CDDP. In this study, the urinary metabolomics approach using liquid chromatography time of flight mass spectrometry (LC-TOF/MS) was developed to assess the toxicity-attenuation effects and corresponding mechanisms of HI on CDDP-exposed rats. As a result, successive administration of HI significantly recovered the decline of body weight and downregulated the abnormal increase of serum creatinine and urea. HI partly restored the CDDP-induced alteration of metabolic profiling back into normal condition. Totally 43 toxicity-attenuation potential biomarkers were screened and tentatively identified, which were involved in important metabolic pathways such as amino acid metabolism, TCA cycle, fatty acid metabolism, vitamin B6 metabolism and purine metabolism. The results clearly revealed that HI could alleviate CDDP-induced nephrotoxicity and improve the disturbed metabolic balance induced by repeated CDDP exposure. The present study provided reliable evidence for the protective effect of HI on CDDP-induced toxicity with the multi-target pharmacological characteristics.
顺铂(CDDP)的副作用,尤其是肾毒性,极大地限制了其在临床化疗中的应用。黄芪注射液(HI)是一种常用的中药黄芪的制剂,似乎是一种有前途的治疗肾毒性的方法,而不会影响 CDDP 的抗肿瘤活性。在这项研究中,采用液相色谱飞行时间质谱(LC-TOF/MS)的尿代谢组学方法来评估 HI 对 CDDP 暴露大鼠的减毒作用及其相应机制。结果表明,连续给予 HI 可显著恢复体重下降,并下调血清肌酐和尿素的异常升高。HI 部分恢复了 CDDP 诱导的代谢谱改变回正常状态。共筛选和初步鉴定出 43 种潜在的减毒生物标志物,这些标志物涉及氨基酸代谢、TCA 循环、脂肪酸代谢、维生素 B6 代谢和嘌呤代谢等重要代谢途径。结果清楚地表明,HI 可以减轻 CDDP 诱导的肾毒性,并改善反复 CDDP 暴露引起的代谢失衡。本研究为 HI 对 CDDP 诱导的毒性的保护作用提供了可靠的证据,具有多靶点的药理特性。