A single-injection targeted metabolomics profiling method for determination of biomarkers to reflect tripterygium glycosides efficacy and toxicity.,Toxicology and Applied Pharmacology

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A single-injection targeted metabolomics profiling method for determination of biomarkers to reflect tripterygium glycosides efficacy and toxicity.
Toxicology and Applied Pharmacology ( IF 3.3 ) Pub Date : 2020-01-14 , DOI: 10.1016/j.taap.2020.114880
Ting Hu ₁ , Chen Shi ₁ , Lihong Liu ₁ , Pengfei Li ₁ , Yuan Sun ₁ , Zhuoling An ₁

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Metabolomics is a powerful tool for studying physiological state of the system. In this study, we proposed a single-injection targeted metabolomics method to identify reliable tripterygium glycosides efficacy and toxicity related biomarkers based on ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Through careful optimization of the UHPLC-MS/MS conditions, a total of 289 metabolites can be quantified in single-injection of 27 min using both positive and negative scanning modes with rapid polarity switching. Tripterygium glycosides is widely used in clinical for its excellent anti-inflammatory and immunosuppressive functions. However, it is the most common drug that can cause hepatotoxicity. In this study, the established metabolomics method was used for determination of biomarkers to reflect tripterygium glycosides efficacy and toxicity. Two different dosages were designed in the animal experiment, including therapeutic dosage and toxic dosage. Statistical analysis based on metabolite concentrations showed that the glutathione metabolism and pyrimidine metabolism were the obvious interfering pathways. This was highly consistent with previous studies. A total of 22 and 47 metabolites were screened as potential biomarkers related to the efficacy and hepatotoxicity of tripterygium glycosides, respectively. Receiver operating characteristic curve (ROC) analysis showed that ten metabolites, including cytosine, 5-methyluridine, deoxyuridine, 5-methylcytidine, deoxycytidine triphosphate (DCTP), keto-glutarate, d-ribose, dihydrofolate, nordeoxycholic acid and isodeoxycholic acid possessed area under the curve (AUC) of 1. The metabolites filtered here can better distinguish tripterygium glycosides treated rats from the control rats compared with the traditional blood indicators of liver function.

中文翻译：

用于确定生物标记物以反映雷公藤多甙的功效和毒性的单次注射靶向代谢组学分析方法。

代谢组学是研究系统生理状态的强大工具。在这项研究中，我们提出了基于超高效液相色谱-串联质谱（UHPLC-MS / MS）的单次注射靶向代谢组学方法，以鉴定可靠的雷公藤多甙功效和毒性相关生物标志物。通过仔细优化UHPLC-MS / MS条件，使用正负极扫描模式和快速极性切换，一次进样27分钟即可定量总共289种代谢物。雷公藤多甙具有出色的抗炎和免疫抑制功能，在临床上被广泛使用。但是，它是最常见的可引起肝毒性的药物。在这个研究中，建立的代谢组学方法用于确定生物标记物，以反映雷公藤多甙的功效和毒性。在动物实验中设计了两种不同的剂量，包括治疗剂量和毒性剂量。基于代谢物浓度的统计分析表明，谷胱甘肽代谢和嘧啶代谢是明显的干扰途径。这与以前的研究高度一致。总共筛选了22种和47种代谢物作为雷公藤多甙的功效和肝毒性的潜在生物标志物。接收者工作特征曲线（ROC）分析显示十种代谢产物，包括胞嘧啶，5-甲基尿苷，脱氧尿苷，5-甲基胞苷，三磷酸脱氧胞苷（DCTP），酮戊二酸，d-核糖，二氢叶酸，

更新日期：2020-01-14

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