1. Metabolomic and sphingolipidomic profiling of human hepatoma cells exposed to widely used pharmaceuticals.
- Author
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Pérez-Cova M, Bedia C, Checa A, Meister I, Tauler R, Wheelock CE, and Jaumot J
- Subjects
- Humans, Hep G2 Cells, Carbamazepine pharmacology, Anti-Bacterial Agents pharmacology, Sphingolipids metabolism, Metabolomics methods, Carcinoma, Hepatocellular metabolism, Carcinoma, Hepatocellular drug therapy, Liver Neoplasms metabolism, Liver Neoplasms drug therapy
- Abstract
Pharmaceutical compounds have become one of the main contaminants of emerging concern (CECs) due to their high usage and increased release into the environment. This study aims to assess the effects caused by three widely consumed hepatotoxic pharmaceutical compounds: an antibiotic (amoxicillin), an antiepileptic (carbamazepine), and an antidepressant (trazodone), on human health when indirectly exposed to toxicologically relevant concentrations (30, 15, and 7.5 μM for amoxicillin and carbamazepine, and 4, 2, and 1 μM for trazodone). A combination of semi-targeted metabolomic and targeted sphingolipid analyses was chosen to unravel the metabolic alterations in human hepatic cells exposed to these CECs at three concentrations for 24 h. HepG2 hepatoma cells were encapsulated in sodium alginate spheroids to improve the physiological relevance of this in vitro approach. Statistical analysis was used to identify the most affected metabolites and sphingolipids for each drug exposure. The results revealed small but significant changes in response to carbamazepine and trazodone exposures, affecting sphingolipid, glycerophospholipid precursors, and amino acid metabolism. Under both drug treatments, a decrease in various ceramide species (related to cell signaling) was observed, along with reduced taurine levels (related to the biosynthesis of bile acid conjugates) and carnitine levels (suggesting an impact on energy production). These and other drug-specific changes indicate that cellular functions in liver cells might be altered under low doses of these CECs, potentially affecting the health of other organs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2024
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