{"title":"Metabolomic and sphingolipidomic profiling of human hepatoma cells exposed to widely used pharmaceuticals","authors":"","doi":"10.1016/j.jpba.2024.116378","DOIUrl":null,"url":null,"abstract":"<div><p>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.</p></div>","PeriodicalId":16685,"journal":{"name":"Journal of pharmaceutical and biomedical analysis","volume":null,"pages":null},"PeriodicalIF":3.1000,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0731708524004187/pdfft?md5=f0ac840ef11f1dc90f3368667ccdf85d&pid=1-s2.0-S0731708524004187-main.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of pharmaceutical and biomedical analysis","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0731708524004187","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, ANALYTICAL","Score":null,"Total":0}
引用次数: 0
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.
期刊介绍:
This journal is an international medium directed towards the needs of academic, clinical, government and industrial analysis by publishing original research reports and critical reviews on pharmaceutical and biomedical analysis. It covers the interdisciplinary aspects of analysis in the pharmaceutical, biomedical and clinical sciences, including developments in analytical methodology, instrumentation, computation and interpretation. Submissions on novel applications focusing on drug purity and stability studies, pharmacokinetics, therapeutic monitoring, metabolic profiling; drug-related aspects of analytical biochemistry and forensic toxicology; quality assurance in the pharmaceutical industry are also welcome.
Studies from areas of well established and poorly selective methods, such as UV-VIS spectrophotometry (including derivative and multi-wavelength measurements), basic electroanalytical (potentiometric, polarographic and voltammetric) methods, fluorimetry, flow-injection analysis, etc. are accepted for publication in exceptional cases only, if a unique and substantial advantage over presently known systems is demonstrated. The same applies to the assay of simple drug formulations by any kind of methods and the determination of drugs in biological samples based merely on spiked samples. Drug purity/stability studies should contain information on the structure elucidation of the impurities/degradants.