Work

Propofol and Thiopental Disrupt Amino Acid and Carnitine Metabolism in HEK-293 Cells: Insights into Mitochondrial Toxicity

Year: 2025

Type: article

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 practices, particularly in high-risk or long-duration clinical scenarios.

Source: Harran Üniversitesi Tıp Fakültesi Dergisi

DOI: 10.35440/hutfd.1719754