Untargeted Metabolomics Studies of H9c2 Cardiac Cells Submitted to Oxidative Stress, β-Adrenergic Stimulation and Doxorubicin Treatment: Investigation of Cardiac Biomarkers

氧化应激、β-肾上腺素刺激和阿霉素治疗下的 H9c2 心脏细胞的非靶向代谢组学研究:心脏生物标志物的研究

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作者:Monica Força Lima, Alan Gonçalves Amaral, Isabela Aparecida Moretto, Franckson Jhonne Torres Neves Paiva-Silva, Flávia Oliveira Borges Pereira, Coral Barbas, Aline Mara Dos Santos, Ana Valéria Colnaghi Simionato, Francisco Javier Rupérez

Abstract

One of the biggest challenges in the search for more effective treatments for diseases is understanding their etiology. Cardiovascular diseases (CVD) are an important example of this, given the high number of deaths annually. Oxidative stress (the imbalance between oxidant and antioxidant species in biological system) is one of the factors responsible for CVD occurrence, demanding extensive investigation. Excess of reactive oxygen species (ROS) are primarily responsible for this condition, and clinical and scientific literature have reported a significant increase in ROS when therapeutic drugs, such as doxorubicin and isoproterenol, are administered. In this context, the aim of this study is the investigation of potential biomarkers that might be associated with oxidative stress in cardiomyocytes. For this purpose, H9c2 cardiomyocytes were submitted to oxidative stress conditions by treatment with doxorubicin (DOX), isoproterenol (ISO) and hydrogen peroxide (PER). Metabolomics analyses of the cell extract and the supernatant obtained from the culture medium were then evaluated by CE-ESI(+)-TOF-MS. Following signal processing, statistical analyses, and molecular features annotations, the results indicate changes in the aspartate, serine, pantothenic acid, glycerophosphocholine and glutathione metabolism in the cell extract.

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