Urinary metabolomics reveals the therapeutic effect of HuangQi Injections in cisplatin-induced nephrotoxic rats.
Urinary metabolomics reveals the therapeutic effect of HuangQi Injections in cisplatin-induced nephrotoxic rats.
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尿代谢组学揭示黄芪注射液对顺铂肾毒性大鼠的治疗作用
DOI：
10.1038/s41598-017-03249-z
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发表时间：
2017-06-15
影响因子：
4.6
通讯作者：
Ju WZ
中科院分区：
文献类型：
--
作者：
Li CY;Song HT;Wang XX;Wan YY;Ding XS;Liu SJ;Dai GL;Liu YH;Ju WZ
顺铂（cisplatin，CDDP）的毒副作用，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）是一种常用的中草药黄芪制剂，在不影响顺铂抗肿瘤活性的前提下，有望成为治疗肾毒性的有效药物。本研究应用液相色谱飞行时间质谱（LC-TOF/MS）技术，建立了尿代谢组学方法，以评价HI对CDDP染毒大鼠的减毒作用及其机制。结果，HI连续给药显著恢复了体重下降，并下调了血清肌酐和尿素的异常升高。HI部分恢复CDDP诱导的代谢谱改变回到正常状态。筛选并初步鉴定出43个潜在减毒生物标志物，它们参与氨基酸代谢、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CDDP重复暴露引起的代谢平衡紊乱。本研究为HI对CDDP毒性的保护作用提供了可靠的证据。
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 medicineAstragali 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.