TY - JOUR T1 - Early Events in the Induction of Rat Hepatic UDP-Glucuronosyltransferases, Glutathione <em>S</em>-Transferase, and Microsomal Epoxide Hydrolase by 1,7-Phenanthroline: Comparison with Oltipraz, <em>tert</em>-Butyl-4-hydroxyanisole, and<em>tert</em>-Butylhydroquinone JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 1018 LP - 1023 VL - 28 IS - 9 AU - John G. Lamb AU - Michael R. Franklin Y1 - 2000/09/01 UR - http://dmd.aspetjournals.org/content/28/9/1018.abstract N2 - Several classes of compounds are able to induce a spectrum of drug-metabolizing enzymes without inducing cytochrome P450s. Examples include antioxidants such as tert-butyl-4-hydroxyanisole and its metabolite tert-butylhydroquinone, dithiolthiones such as oltipraz, and N-heterocycles such as 1,7-phenanthroline. The events associated with induction of UDP-glucuronosyltransferases (UGT), glutathioneS-transferases, and microsomal epoxide hydrolase after a single oral dose of these agents have been compared. No agent significantly elevated any of these enzyme activities within 24 h, but oltipraz and 1,7-phenanthroline significantly increased glutathioneS-transferase and UGT activities by 48 h. 1,7-Phenanthroline and oltipraz showed generally similar time-course responses of drug-metabolizing enzyme mRNAs; little change from control at 6 h followed by significant and maximal increases 12 to 18 h after treatment. Maximal mRNA changes for 1,7-phenanthroline and oltipraz were of similar magnitude and clustered around 4-fold for most enzymes. With the exception of one UGT isozyme (UGT1A1), the elevations in mRNA were blocked by prior administration of actinomycin D, indicative of a transcription-dependent response. Neithertert-butyl-4-hydroxyanisole nortert-butylhydroquinone caused a statistically significant increase in any mRNA examined at any time point. The American Society for Pharmacology and Experimental Therapeutics ER -