Anesthesia-Induced Ferroptosis: Bidirectional Regulation and Molecular Mechanisms in Cardio-Cerebral Injury

Area of Science:

• Anesthesiology
• Cellular Biology
• Biochemistry

Background:

• Perioperative anesthetic agents like sevoflurane, propofol, and dexmedetomidine may cause cardio-cerebral injury.
• This injury is linked to ferroptosis, an iron-dependent cell death pathway.
• Understanding the mechanisms of anesthetic-induced injury is crucial for patient safety.

Purpose of the Study:

• Introduce the "Molecular Switches" concept to explain tissue-specific anesthetic effects on ferroptosis.
• Propose novel anesthetic strategies for perioperative cardio-cerebral protection based on this concept.
• Address challenges in clinical translation and suggest future research directions.

Main Methods:

• Conceptual framework development based on existing literature.
• Analysis of molecular mechanisms regulating ferroptosis, including GPX4, SLC7A11, and ACSL4.
• Review of organ-specific factors influencing anesthetic-induced ferroptosis in heart and brain.
• Discussion of potential therapeutic targets and strategies.

Main Results:

• Anesthetics act as tissue-specific "Molecular Switches" that can promote or inhibit ferroptosis.
• Cardio-cerebral organs exhibit unique molecular configurations making them susceptible to ferroptosis.
• Targeting the Nrf2/GPX4/SLC7A11 axis and inhibiting ACSL4 are potential protective strategies.
• Myocardial protection requires mitochondrial recovery and iron efflux modulation; cerebroprotection needs neuronal iron homeostasis and BBB integrity.

Conclusions:

• The "Molecular Switches" framework offers novel insights into perioperative cardio-cerebral protection.
• Personalized anesthetic protocols, targeted drug delivery, and AI-driven models are promising for clinical application.
• Further research is needed to overcome challenges in drug specificity, polypharmacy, and biomarker development.