@article{article_1719754, title={Propofol and Thiopental Disrupt Amino Acid and Carnitine Metabolism in HEK-293 Cells: Insights into Mitochondrial Toxicity}, journal={Harran Üniversitesi Tıp Fakültesi Dergisi}, volume={22}, year={2025}, author={Pehlivan, Veli Fahri and Pehlivan, Başak and Duran, Erdoğan and Koyuncu, İsmail and Erdoğdu, Hamza and Binici, Orhan and Karahan, Mahmut Alp and Şengel, Abdulhakim and Atlas, Ahmet}, keywords={Propofol, Thiopental, Metabolomics, HEK-293 cells, Cellular toxicity}, abstract={Background: Propofol and thiopental are widely used intravenous anesthetics with rapid onset and short duration of action. However, their impact on mitochondrial integrity and cellular metabolism under high-dose exposure remains incompletely characterized.
Materials and Methods: This study employed a metabolomics-based approach, we examined the dose-dependent effects of propofol and thiopental on intracellular amino acid and carnitine metabolism in HEK-293 cells. Cell viability was assessed by MTT assay, and targeted quantification of metabolites was performed via liquid chromatography-mass spectrometry (MS)/MS. All metabolite levels were normalized to total protein content to account for cellular variability.
Results: Both anesthetics caused significant, dose-dependent metabolic alterations. Propofol led to marked depletion of key amino acids (glutamine, alanine, aspartate) and acylcarnitines (C0, C2), indicating compromised mitochondrial β-oxidation and redox homeostasis. Thiopental showed higher cytotoxicity at lower concentrations but induced less disruption in carnitine pathways. Effect size analysis (Cohen’s d) confirmed large-to-extreme differences, particularly at 200 μg/mL, underscoring distinct metabolic footprints for each agent.
Conclusions: Propofol and thiopental elicit agent-specific metabolic signatures in renal cells, with implications for mitochondrial dysfunction and anesthetic-induced toxicity. These findings support the utility of targeted metabolomic profiling in guiding safer anesthetic practic}, number={4}, publisher={Harran University}, organization={Harran University Scientific Research Projects Unit}