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

Öz

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.

Anahtar Kelimeler

• Propofol
• Thiopental
• Metabolomics
• HEK-293 cells
• Cellular toxicity

Propofol ve Tiyopental, HEK-293 Hücrelerinde Amino Asit ve Karnitin Metabolizmasını Bozar: Mitokondriyal Toksisiteye Dair Bulgular

Öz

Amaç: Propofol ve tiyopental, hızlı başlangıç ve kısa etki süresi ile yaygın olarak kullanılan intravenöz anestezik ajanlardır. Ancak bu ajanların yüksek doz maruziyet altında mitokondri bütünlüğü ve hücresel metabolizma üzerindeki etkileri yeterince anlaşılamamıştır. Materyal ve metod: Bu çalışmada, metabolomik temelli bir yaklaşımla propofol ve tiyopentalin HEK-293 hücrelerinde hücre içi amino asit ve karnitin metabolizması üzerindeki doz bağımlı etkileri incelenmiştir. Hücre canlılığı MTT testi ile değerlendirilmiş; hedeflenmiş metabolit düzeyleri sıvı kromatografisi-kütle spektrometresi (MS)/MS yöntemiyle nicel olarak analiz edilmiştir. Metabolit düzeyleri toplam hücresel protein miktarına normalize edilmiştir. Bulgular: Her iki anestezik ajan da anlamlı ve doz bağımlı metabolik değişikliklere yol açmıştır. Propofol, temel amino asitler (glutamin, alanin, aspartat) ve asilkarnitinlerde (C0, C2) belirgin azalma oluşturmuş; bu da mitokondriyal β-oksidasyon ve redoks homeostazında bozulmaya işaret etmektedir. Tiyopental daha düşük konsantrasyonlarda daha yüksek sitotoksisite göstermiş ancak karnitin metabolizmasında daha az bozulmaya neden olmuştur. Etki büyüklüğü analizi (Cohen’s d), özellikle 200 μg/mL dozda olmak üzere, iki ajan arasında büyükten aşırıya değişen farklar olduğunu doğrulamıştır. Sonuç: Propofol ve tiyopental, böbrek hücrelerinde ajanlara özgü metabolik izler oluşturmakta olup bu farklılıklar mitokondriyal disfonksiyon ve anestezi kaynaklı toksisite açısından klinik önem taşımaktadır. Elde edilen bulgular, hedeflenmiş metabolomik profil analizlerinin, özellikle yüksek riskli veya uzun süreli anestezik maruziyet gerektiren durumlarda daha güvenli anestezi uygulamalarını yönlendirmede değerli bir araç olabileceğini göstermektedir.

Anahtar Kelimeler

• Propofol
• Tiyopental
• Metabolomik
• HEK-293 hücreleri
• Hücresel toksisite

Kaynakça

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