Metabolic activation of 1-naphthol by rat liver microsomes to 1,4-naphthoquinone and covalent binding species.
1-Naphthol was metabolized by rat liver microsomes, in the presence of an NADPH-generating system, both to methanol-soluble metabolites including 1,4-naphthoquinone and an uncharacterized product(s) (X) and also to covalently bound products. NADH was much less effective as an electron donor than NADPH. Metyrapone, SKF 525-A and carbon monoxide all inhibited the metabolism of 1-naphthol to 1,4-naphthoquinone and to covalently bound products suggesting the involvement of cytochrome P-450 in at least one step in the metabolic activation of 1-naphthol to reactive products. Ethylene diamine, which reacts selectively with 1,2-naphthoquinone but not 1,4-naphthoquinone, did not affect the covalent binding whereas glutathione, which reacts with both naphthoquinones, caused an almost total inhibition of covalent binding. These and other results suggested that 1,4-naphthoquinone, or a metabolite derived from it, was responsible for most of the covalent binding observed and that little if any of the binding was due to 1,2-naphthoquinone.
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D001711:Biotransformation; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology; D005029:Ethylenediamines / Q000494:pharmacology; D005978:Glutathione / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D009284:Naphthols / Q000378:metabolism*; D009285:Naphthoquinones / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013482:Superoxide Dismutase / Q000494:pharmacology
D005029:Ethylenediamines; D009284:Naphthols; D009285:Naphthoquinones; C029350:1-naphthol; C031234:ethylenediamine; D003577:Cytochrome P-450 Enzyme System; D013482:Superoxide Dismutase; D005978:Glutathione; D001205:Ascorbic Acid; C035342:1,4-naphthoquinone