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Metabolomic and sphingolipidomic profiling of human hepatoma cells exposed to widely used pharmaceuticals.
Pérez-Cova, Miriam; Bedia, Carmen; Checa, Antonio; Meister, Isabel; Tauler, Romà; Wheelock, Craig E; Jaumot, Joaquim.
Afiliación
  • Pérez-Cova M; Department of Environmental Chemistry, IDAEA-CSIC, Jordi Girona 18-26, Barcelona E08034, Spain; Department of Chemical Engineering and Analytical Chemistry, University of Barcelona, Diagonal 647, Barcelona, Barcelona E08028, Spain.
  • Bedia C; Department of Environmental Chemistry, IDAEA-CSIC, Jordi Girona 18-26, Barcelona E08034, Spain.
  • Checa A; Unit of Integrative Metabolomics, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.
  • Meister I; Unit of Integrative Metabolomics, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden; Gunma University Initiative for Advanced Research (GIAR), Gunma University, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
  • Tauler R; Department of Environmental Chemistry, IDAEA-CSIC, Jordi Girona 18-26, Barcelona E08034, Spain.
  • Wheelock CE; Unit of Integrative Metabolomics, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden; Gunma University Initiative for Advanced Research (GIAR), Gunma University, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan; Department of Respiratory Medicine and Allergy, Karolinska
  • Jaumot J; Department of Environmental Chemistry, IDAEA-CSIC, Jordi Girona 18-26, Barcelona E08034, Spain. Electronic address: joaquim.jaumot@idaea.csic.es.
J Pharm Biomed Anal ; 249: 116378, 2024 Oct 15.
Article en En | MEDLINE | ID: mdl-39074424
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Esfingolípidos / Carcinoma Hepatocelular / Metabolómica / Neoplasias Hepáticas Límite: Humans Idioma: En Revista: J Pharm Biomed Anal Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Esfingolípidos / Carcinoma Hepatocelular / Metabolómica / Neoplasias Hepáticas Límite: Humans Idioma: En Revista: J Pharm Biomed Anal Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido