Anesthetic-Induced Disruption of Amino Acid and Carnitine Profiles: A Metabolomic Comparison of Propofol and Thiopental in Hepatocytes

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Background/Objectives: Propofol and Thiopental are widely used anesthetic agents, yet their cumulative and high-dose effects on hepatic metabolism remain insufficiently characterized. This study aimed to evaluate the impact of supra-therapeutic concentrations of these agents on carnitine and amino acid metabolism in AML12 hepatocytes, with a focus on their toxicometabolic profiles. Methods: AML12 mouse hepatocytes were exposed to escalating concentrations (2.5–500 µg/mL) of Propofol and Thiopental to assess cytotoxicity. IC50 values (~255 µg/mL for both) were determined, and two high-dose concentrations (100 µg/mL and 200 µg/mL) were selected for metabolic profiling. Cell viability was assessed via the MTT assay. Intracellular carnitine and amino acid levels were quantified using LC-MS/MS. Statistical analyses included one-way ANOVA with post hoc tests, unpaired t-tests, and effect size estimations (Cohen’s d). Results: Propofol significantly suppressed carnitine metabolism in a dose-dependent manner, with a 79% reduction in free carnitine (C0), indicative of impaired mitochondrial β-oxidation. Thiopental, however, preserved or partially restored several acylcarnitines, including C16:1. While both agents reduced intracellular amino acid levels, 200 µg/mL Thiopental partially restored key metabolites such as glutamine, alanine, and histidine. Propofol exhibited broader metabolic suppression. Effect size analysis further confirmed the stronger inhibitory impact of Propofol. Conclusion: Although the concentrations used exceed typical clinical plasma levels, they may reflect prolonged or high-dose exposure scenarios observed in ICU settings. The findings highlight distinct toxicometabolic signatures for each agent and underscore the utility of metabolite profiling in modeling anesthetic-induced hepatic stress and guiding anesthetic selection in vulnerable populations.

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