Reactions of Glutathione with Oxidative Intermediates of Acetaminophen
Acetaminophen (4’-hydroxyacetanilide) is an analgesic and antipyretic drug, which is reportedly safe at low doses, but when administered in large doses causes hepatic necrosis and renal damage in both humans and laboratory animals (1–8). Acetaminophen is thought to be metabolized to reactive intermediate(s) that cause toxic reactions and current thinking suggests that acetaminophen may be activated via a one-electron oxidation mechanisms to give N-acetyl-p-benzosemiquinone imine (9) or a two-electron oxidation to give N-acetyl-p-benzoquinone imine (10).
KeywordsHorseradish Peroxidase Incubation Mixture Hepatic Necrosis Quinone Imine Benzoquinone Imine
Unable to display preview. Download preview PDF.
- 1.E. M. Boyd and G.M. Bereczky, Liver necrosis from paracetamol, Brit. J. Biochem. 26: 606–607 (1966).Google Scholar
- 11.D. d. Potter, D. W. Miller, and J. A. Hinson, Identification of acetaminophen polymerization products catalyzed by horseradish peroxidase, J. Biol. Chem. in press (1985).Google Scholar
- 12.D. W. Potter, D. W. Miller, and J. A. Hinson, Horseradish peroxidase-catalyzed oxidation of acetaminophen to intermediates that form polymers or conjugate with glutathione, Submitted (1985).Google Scholar
- 13.D. C. Dahlia and S. D. Nelson, Synthesis, decomposition kinetics, and preliminary toxicological studies of pure N-acetyl-pbenzoquinone imine, a proposed toxic metabolite of acetaminophen, J. Med. Chem. 24: 988–993 (1982).Google Scholar
- 20.I. Yamazaki, One-electron and two-electron transfer mechanisms in enzymatic oxidation-reduction reactions, Advan. in Biophys. 2:33–76 (1971).Google Scholar