Validation of biomarkers in cardiotoxicity induced by Periplocin on neonatal rat cardiomyocytes using UPLC-Q-TOF/MS combined with a support vector machine
Validation of biomarkers in cardiotoxicity induced by Periplocin on neonatal rat cardiomyocytes using UPLC-Q-TOF/MS combined with a support vector machine
复制标题
使用 UPLC-Q-TOF/MS 结合支持向量机验证 Periplocin 对新生大鼠心肌细胞的心脏毒性生物标志物
DOI：
10.1016/j.jpba.2016.02.014
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发表时间：
2016-05-10
影响因子：
3.4
通讯作者：
Zhang, Yanjun
中科院分区：
文献类型：
--
作者：
Li, Aizhu;Guo, Xuejun;Zhang, Yanjun
杠柳（Periploca sepium Bge.）的根，临床应用广泛。杠柳毒苷是杠柳毒中强心苷类成分之一，使用不当易引起心脏毒性。为了评价杠柳毒苷的毒性，我们采用UPLC-Q-TOF/MS技术研究了高、低剂量杠柳毒苷（0.2mmol/L、0.4mmol/L）对乳鼠心肌细胞代谢的影响。最后，我们通过多变量统计分析确定了11个与毒性相关的生物标志物。一个“监督”支持向量机（SVM）的研究被用来优化和验证这些生物标志物的可靠性。在这些生物标志物中，包括肉毒碱、乙酰肉毒碱、lysoPC（16：0）、脯氨酸、谷氨酸、焦谷氨酸、亮氨酸、泛酸、色氨酸、吲哚丙烯酸和柠檬酸在内的所有生物标志物均随剂量的增加而呈下降趋势。此外，途径分析表明，这些代谢产物与氨基酸代谢、能量代谢和鞘脂代谢有关，这有助于进一步了解香加鱼的毒性机制及其临床安全性。此外，我们证明了基于UPLC-Q-TOF/MS的代谢组学方法是一个强大的工具，并提供了一个有前途的方法来评估中药的毒性和药物安全性筛选。(C)2016爱思唯尔B. V.保留所有权利。
Corex Periplocae (the root of Periploca sepium Bge) has been widely used in clinics. Periplocin, as one of the components of cardiac glycosides in Corex Periplocae, easily triggers cardiotoxicity when used improperly. To evaluate the toxicity of Periplocin, we used UPLC-Q-TOF/MS to investigate metabolic profiles on neonatal rat cardiomyocytes exposed to high and low doses of Periplocin (0.2 mmol/L, 0.4 mmol/L). Finally, we identified 11 biomarkers associated with toxicity through multivariate statistical analysis. A "supervised" Support Vector Machine (SVM) study was used to optimize and verify the reliability of these biomarkers. In these biomarkers, all biomarkers, including carnitine, acetylcarnitine, lysoPC(16:0), proline, glutamic acid, pyroglutamic acid, leucine, pantothenic acid, tryptophan, indoleacrylic acid and citric acid, revealed a downward trend with the increase of dosage. Moreover, pathway analysis showed that these metabolites were associated with amino acid metabolism, energy metabolism and sphingolipid metabolism, which contributes to a further understanding of the toxicity mechanism of Corex Periplocae and its clinical safety. Additionally, we demonstrate that an UPLC-Q-TOF/MS-based metabolomic approach is a powerful tool and provides a promising approach for assessing the toxicity of traditional Chinese medicine and drug safety screening. (C) 2016 Elsevier B.V. All rights reserved.