PT  - JOURNAL ARTICLE
AU  - Rosen, G M
AU  - Rauckman, E J
AU  - Ellington, S P
AU  - Dahlin, D C
AU  - Christie, J L
AU  - Nelson, S D
TI  - Reduction and glutathione conjugation reactions of N-acetyl-p-benzoquinone imine and two dimethylated analogues.
DP  - 1984 Jan 01
TA  - Molecular Pharmacology
PG  - 151--157
VI  - 25
IP  - 1
4099  - http://molpharm.aspetjournals.org/content/25/1/151.short
4100  - http://molpharm.aspetjournals.org/content/25/1/151.full
SO  - Mol Pharmacol1984 Jan 01; 25
AB  - N-Acetyl-3,5-dimethyl-p-benzoquinone imine, N-acetyl-2,6-dimethyl-p-benzoquinone imine, and N-acetyl-p-benzoquinone imine were synthesized via the oxidation of 3,5-dimethylacetaminophen, 2,6-dimethylacetaminophen, and acetaminophen, respectively. All three quinone imines were rapidly reduced to their corresponding semiquinone imines by NADPH-cytochrome P-450 reductase. All three benzoquinone imines underwent comproportionation with their respective phenols to yield the corresponding semiquinone imines, which in the presence of oxygen gave superoxide. Identification of this latter free radical was based on spin-trapping techniques. Reduced GSH was found to be an excellent nucleophile toward N-acetyl-2,6-dimethyl-p-benzoquinone imine, whereas this thiol behaved as a one-electron reductant toward N-acetyl-3,5-dimethyl-p-benzoquinone imine. Finally, GSH was determined to act as both a nucleophile and a reductant toward N-acetyl-p-benzoquinone imine.