Convergent mitochondrial toxicity of fluorinated agents in oncological anaesthesia: sevoflurane, 5-fluorouracil, and the ACOD1/itaconate immune axis - Takeaways - MDSpire

Convergent mitochondrial toxicity of fluorinated agents in oncological anaesthesia: sevoflurane, 5-fluorouracil, and the ACOD1/itaconate immune axis

  • By

  • Ivan N. Dushin

  • May 20, 2026

  • 0 min

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  • 1

    ACOD1-derived itaconate regulates tumor immune surveillance by suppressing inflammatory gene expression and limiting CD8⁺ T-cell infiltration.

  • 2

    Sevoflurane and 5-fluorouracil may inhibit aconitase 2, depleting cis-aconitate and disrupting itaconate-dependent immune regulation.

  • 3

    5-fluorouracil generates fluoroacetate, which inhibits aconitase and can lead to type B lactic acidosis and encephalopathy.

  • 4

    Sevoflurane metabolism by CYP2E1 produces fluorinated intermediates that may inhibit aconitase, affecting mitochondrial function.

  • 5

    Pre-operative genotyping for DPYD and ACOD1 variants is suggested to guide anesthetic technique selection in oncological patients.

Original Source(s)

Convergent mitochondrial toxicity of fluorinated agents in oncological anaesthesia: sevoflurane, 5-fluorouracil, and the ACOD1/itaconate immune axis

  • by Ivan N. Dushin

  • May 20, 2026

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