Reactive oxygen species and peroxynitrite in acetaminophen-induced liver injury: Lipid peroxidation and ferroptosis-like cell death - PubMed
3 months ago
- #Liver Injury
- #Acetaminophen
- #Ferroptosis
- Acetaminophen (APAP) overdose is a key model for studying drug hepatotoxicity and acute liver failure.
- Mechanisms of APAP-induced liver injury include cytochrome P450 2E1-mediated reactive metabolite formation, glutathione depletion, and mitochondrial dysfunction.
- Oxidant stress and peroxynitrite formation lead to mitochondrial protein nitration and cell necrosis.
- The mode of cell death in APAP toxicity overlaps with apoptosis, necroptosis, pyroptosis, and recently debated ferroptosis.
- APAP-induced necrosis differs from ferroptosis in glutathione depletion patterns, oxidant stress mechanisms, and limited lipid peroxidation.
- Exogenous ferrous iron can induce lipid peroxidation and switch APAP-induced cell death to ferroptosis-like death.
- Under normal conditions, APAP hepatotoxicity does not involve ferroptosis but can be triggered by co-ingested supplements.