Dataset related to the article "Untargeted Metabolomics to Go beyond the Canonical Effect of Acetylsalicylic Acid"

This record contains raw data related to the article “Untargeted Metabolomics to Go beyond the Canonical Effect of Acetylsalicylic Acid" <strong>Abstract</strong> Given to its ability to irreversibly acetylate the platelet cyclooxygenase-1 enzyme, acetylsalicylic acid (ASA) is successfully employed for the prevention of cardiovascular disease. Recently, an antitumoral effect of ASA in colorectal cancer has been increasingly documented. However, the molecular and metabolic mechanisms by which ASA exerts such effect is largely unknown. Using a new, untargeted liquid chromatography-mass spectrometry approach, we have analyzed urine samples from seven healthy participants that each ingested 100 mg of ASA once daily for 1 week. Of the 2007 features detected, 25 metabolites differing after ASA ingestion (nominal <em>p</em> &lt; 0.05 and variable importance in projection (VIP) score &gt; 1) were identified, and pathway analysis revealed low levels of glutamine and of metabolites involved in histidine and purine metabolisms. Likewise, consistent with an altered fatty acid <em>β</em>-oxidation process, a decrease in several short- and medium-chain acyl-carnitines was observed. An abnormal <em>β</em>-oxidation and a lower than normal glutamine availability suggests reduced synthesis of acetyl-Co-A, as they are events linked to one another and experimentally related to ASA antiproliferative effects. While giving an example of how untargeted metabolomics allows us to explore new clinical applications of drugs, the present data provide a direction to be pursued to test the therapeutic effects of ASA-e.g., the antitumoral effect-beyond cardiovascular protection.本数据集收录与《非靶向代谢组学探究乙酰水杨酸的非经典效应》一文相关的原始实验数据。摘要：鉴于其能够不可逆地乙酰化血小板环氧化酶-1（platelet cyclooxygenase-1）的特性，乙酰水杨酸（acetylsalicylic acid, ASA）已被成功应用于心血管疾病的预防。近年来，乙酰水杨酸在结直肠癌中的抗肿瘤效应愈发得到证实，但其发挥该效应的分子与代谢机制仍未被完全阐明。本研究采用全新的非靶向液相色谱-质谱（liquid chromatography-mass spectrometry, LC-MS）联用分析方法，对7名健康受试者的尿液样本进行了分析——受试者每日单次口服100 mg乙酰水杨酸，持续1周。在检测到的2007个特征峰中，共有25种代谢物在乙酰水杨酸摄入后出现显著差异（名义p值<0.05，投影变量重要性（variable importance in projection, VIP）评分>1）；代谢通路分析显示，受试者体内谷氨酰胺以及参与组氨酸和嘌呤代谢的代谢物水平显著下调。类似地，与脂肪酸β-氧化（fatty acid β-oxidation）过程紊乱相一致，多种短链和中链酰基肉碱的水平亦出现显著降低。异常的β-氧化过程以及谷氨酰胺可用性低于正常水平，提示乙酰辅酶A（acetyl-CoA）的合成减少——上述事件彼此关联，且经实验证实与乙酰水杨酸的抗增殖效应密切相关。本研究既为非靶向代谢组学技术在药物全新临床应用场景中的探索提供了范例，同时也为验证乙酰水杨酸在心血管保护之外的治疗效应（如抗肿瘤效应）指明了可行的研究方向。