In vitro effects of acetaminophen metabolites and analogs on the respiration of mouse liver mitochondria

Acetaminophen, an analgesic and antipyretic, is toxic in overdose to liver and kidney. The effects on mitochondrial respiration of acetaminophen, its less toxic analog, 3-hydroxyacetanilide, and metabolites which arise from these compounds have been investigated. The parent compounds inhibited NADH-linked respiration reversibly, whereas the metabolites inhibit all mitochondrial respiration, apparently in the Complex III region of the respiratory chain. The quinone derivatives, 4-acetamido-o-benzoquinone and 2-acetamido-p-benzoquinone, are the best inhibitors, with the onset of inhibition dependent on active respiration, suggesting interaction of these compounds with oxidized components of the electron transport chain.