Department of Integrative Genomics, Tohoku University Tohoku Medical Megabank Organization, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8573, Japan; Medical Biochemistry, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan.
Department of Integrative Genomics, Tohoku University Tohoku Medical Megabank Organization, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8573, Japan; Advanced Research Center for Innovations in Next-Generation Medicine, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8573, Japan.
Drug Metab Pharmacokinet. 2021 Apr;37:100373. doi: 10.1016/j.dmpk.2020.11.008. Epub 2020 Dec 24.
Metabolomics has been widely used for investigating the biological functions of disease expression and has the potential to discover biomarkers in circulating biofluids or tissue extracts that reflect in phenotypic changes. Metabolic profiling has advantages because of the use of unbiased techniques, including multivariate analysis, and has been applied in pharmacological studies to predict therapeutic and adverse reactions of drugs, which is called pharmacometabolomics (PMx). Nuclear magnetic resonance (NMR)- and mass spectrometry (MS)-based metabolomics has contributed to the discovery of recent disease biomarkers; however, the optimal strategy for the study purpose must be selected from many established protocols, methodologies and analytical platforms. Additionally, information on molecular localization in tissue is essential for further functional analyses related to therapeutic and adverse effects of drugs in the process of drug development. MS imaging (MSI) is a promising technology that can visualize molecules on tissue surfaces without labeling and thus provide localized information. This review summarizes recent uses of MS-based global and wide-targeted metabolomics technologies and the advantages of the MSI approach for PMx and highlights the PMx technique for the biomarker discovery of adverse drug effects.
代谢组学已被广泛用于研究疾病表达的生物学功能，并有潜力在循环生物流体或组织提取物中发现反映表型变化的生物标志物。代谢组学分析具有使用无偏技术（包括多变量分析）的优势，已应用于药理学研究中，以预测药物的治疗和不良反应，这被称为药物代谢组学（PMx）。基于核磁共振（NMR）和质谱（MS）的代谢组学有助于发现最近的疾病生物标志物；然而，必须从许多已建立的方案、方法和分析平台中选择最适合研究目的的策略。此外，关于分子在组织中的定位的信息对于药物开发过程中与药物治疗和不良反应相关的进一步功能分析至关重要。MS 成像（MSI）是一种很有前途的技术，它可以在不进行标记的情况下对组织表面的分子进行可视化，从而提供局部信息。本文综述了基于 MS 的全局和广泛靶向代谢组学技术的最新应用，以及 MSI 方法在 PMx 中的优势，并强调了 PMx 技术在发现药物不良反应生物标志物方面的应用。
