What is the very potent oxidant responsible for acetaminophen’s toxicity?
Peroxynitrite. Protein adducts in mitochondria trigger superoxide formation which eventually leads to phosphorylation of c-jun N-terminal kinase (JNK) which triggers further impairment of the electron transport chain which leads to mitochondrial superoxide formation through complex I and III. The superoxide radical rapidly reacts with nitric oxide and forms peroxynitrite, a very potent oxidant.
Akakpo JY et al. Comparing N-acetylcysteine and 4-methylpyrazole as antidotes for acetaminophen overdose. Archives of Toxicology 2022. Published online 3 Jan 2022. https://doi.org/10.1007/s00204-021-03211-z