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Plasma metabolic profiling analysis of neurotoxicity induced by oxaliplatin using metabonomics and multivariate data analysis

机译:用代谢组学和多元数据分析法分析奥沙利铂引起的神经毒性的血浆代谢谱分析

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摘要

Oxaliplatin is a third generation antitumor agent, which is often used in treating advanced colorectal cancer, but the use of oxaliplatin is limited by its side effects, especially peripheral nerve toxicity. Metabonomics techniques, as a holistic analytical technique, could provide basic information on the metabolic profile of biological fluids during drug administration. In this study, we used the ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) technique to analyze rat plasma samples collected seven days after oxaliplatin administration. The changes of metabolites in plasma samples were evaluated by principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA), and 15 kinds of neurotoxicity-related biomarkers were screened. The metabolic pathways of interference involved amino acid biosynthesis and metabolism, glycerophospholipid metabolism, sphingolipid metabolism and so on. The biomarkers found in this study are significant for the study of neurotoxicity.
机译:奥沙利铂是第三代抗肿瘤药,通常用于治疗晚期结直肠癌,但奥沙利铂的使用受到其副作用(尤其是周围神经毒性)的限制。代谢组学技术作为一种整体分析技术,可以在给药过程中提供有关生物体液代谢概况的基本信息。在这项研究中,我们使用超高效液相色谱结合四极杆飞行时间质谱(UPLC-Q-TOF / MS)技术分析了奥沙利铂给药后7天收集的大鼠血浆样品。通过主成分分析(PCA)和偏最小二乘判别分析(PLS-DA)评估血浆样品中代谢物的变化,并筛选出15种与神经毒性相关的生物标记。干扰的代谢途径涉及氨基酸的生物合成和代谢,甘油磷脂代谢,鞘脂代谢等。在这项研究中发现的生物标志物对于神经毒性的研究具有重要意义。

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