RT Journal Article
SR Electronic
T1 Metabolism of 2,6-dimethylnaphthalene by rat liver microsomes and effect of its administration on glutathione depletion in vivo.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 724
OP 732
VO 14
IS 6
A1 Shamsuddin, Z A
A1 Rahimtula, A D
YR 1986
UL http://dmd.aspetjournals.org/content/14/6/724.abstract
AB Metabolism of the environmental contaminant 2,6-dimethylnaphthalene (2,6-DMN) by rat liver microsomes and an NADPH-regenerating system led to the formation of three ring oxidation metabolites--2,6-dimethyl-3-naphthol, 2,6-dimethyl-3,4-naphthoquinone, and 3,4-dihydro-3,4-dihydroxy-2,6-dimethylnaphthalene--and one side chain oxidation metabolite--2-hydroxymethyl-6-methylnaphthalene. In addition, one metabolite remained unidentified. Pretreatment of rats with phenobarbital, 3-methylcholanthrene, Prudhoe Bay crude oil, or 2,6-DMN enhanced the rate of microsomal metabolism of 2,6-DMN 2-6-fold and significantly altered the metabolite profile. Liver microsomes from variously pretreated rats also enhanced the irreversible binding of 2,6-DMN[8-14C]N to microsomal protein. This binding to protein was inhibited by glutathione in a concentration-dependent manner. In vivo administration of 2,6-DMN to untreated rats led to a time-dependent depletion of hepatic glutathione levels. Both the rate and the extent of glutathione depletion were significantly enhanced in 3-methylcholanthrene-pretreated rats but not in phenobarbital-pretreated rats.