4.6 Article

Evaluation of Cocaine Effect on Endogenous Metabolites of HepG2 Cells Using Targeted Metabolomics

Journal

MOLECULES
Volume 26, Issue 15, Pages -

Publisher

MDPI
DOI: 10.3390/molecules26154610

Keywords

cocaine toxicity; targeted metabolomics; HepG2; liquid chromatography; mass spectrometry

Funding

  1. European Union (European Social FundESF) through the Operational Programme Human Resources Development, Education and Lifelong Learning [MIS-5000432]

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This study evaluated the effect of cocaine on human liver cancer cell lines and revealed the predominant impact of cocaine on the metabolic pathways of alanine, aspartate, and glutamate. Targeted metabolomics identified changes in metabolites upon cocaine administration, but deciphering the exact cocaine cytotoxic mechanism remains challenging.
Cocaine toxicity has been a subject of study because cocaine is one of the most common and potent drugs of abuse. In the current study the effect of cocaine on human liver cancer cell line (HepG2) was assessed. Cocaine toxicity (IC50) on HepG2 cells was experimentally calculated using an XTT assay at 2.428 mM. The metabolic profile of HepG2 cells was further evaluated to investigate the cytotoxic activity of cocaine at 2 mM at three different time points. Cell medium and intracellular material samples were analyzed with a validated HILIC-MS/MS method for targeted metabolomics on an ACQUITY Amide column in gradient mode with detection on a triple quadrupole mass spectrometer in multiple reaction monitoring. About 106 hydrophilic metabolites from different metabolic pathways were monitored. Multivariate analysis clearly separated the studied groups (cocaine-treated and control samples) and revealed potential biomarkers in the extracellular and intracellular samples. A predominant effect of cocaine administration on alanine, aspartate, and glutamate metabolic pathway was observed. Moreover, taurine and hypotaurine metabolism were found to be affected in cocaine-treated cells. Targeted metabolomics managed to reveal metabolic changes upon cocaine administration, however deciphering the exact cocaine cytotoxic mechanism is still challenging.

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