Acetaminophen‐Induced Hepatotoxicity: Role of Metabolic Activation, Reactive Oxygen/Nitrogen Species, and Mitochondrial Permeability Transition
作者： Jack A. Hinson , Angela B. Reid , Sandra S. McCullough , Laura P. James
关键词: Mitochondrial permeability transition pore 、 Reactive nitrogen species 、 Chemistry 、 Nitric oxide 、 Biochemistry 、 Oxidative stress 、 Reactive oxygen species 、 Superoxide 、 Nitrotyrosine 、 Peroxynitrite
摘要: Large doses of the analgesic acetaminophen cause centrilobular hepatic necrosis in man and experimental animals. It has been previously shown that is metabolically activated by CYP enzymes to N-acetyl-p-benzoquinone imine. This species normally detoxified GSH, but following a toxic dose GSH depleted metabolite covalently binds number different proteins. Covalent binding occurs only cells developing necrosis. Recently we showed these also contain nitrated tyrosine residues. Nitrotyrosine mediated peroxynitrite, reactive nitrogen formed rapid reaction between nitric oxide superoxide GSH. Thus, toxicity with increased oxygen/nitrogen stress. manuscript will review current data on covalent binding, stress, mitochondrial permeability transition, mechanism both leads
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