Abstract
Various parameters of drug metabolism were measured in rats following a single intraperitoneal injection of cadmium acetate dihydrate (2.0 mg/kg; 7.5 µmoles/kg). Three days after treatment with Cd2+, the hexobarbital-induced sleeping time was increased to 240% of control; the microsomal contents of cytochromes P-450 and b5 were decreased by 44% and 27%, respectively. Seven days after treatment, the contents of cytochromes P-450 and b5 had partially returned to normal but each was 15-20% below control levels. Aminopyrine demethylase activity in hepatic microsomes was decreased by 47% and 37% at 3 and 7 days, respectively, after treatment with Cd2+; aniline hydroxylase was decreased by 32% and 23% at 3 and 7 days, respectively. Cadmium, given 3 days prior to injection of [3H]δ-aminolevulinic acid, decreased the half-life of the heme in CO-binding particles (microsomes devoid of cytochrome b5) from 8 hr to less than 2.5 hr in the fast-phase component, and from 60 hr to 32 hr in the slow-phase component. The greatest increase in microsomal heme oxygenase (to 350% of control) occurred 36-48 hr after treatment with Cd2+, and the enzymatic activity returned essentially to normal at 7 days. The activity of biliverdin reductase of the cytosol was not altered 3 or 7 days after treatment with Cd2+.
ACKNOWLEDGMENTS We wish to express our appreciation to Dr. Gertrude B. Elion for her encouragement and support of this project; Dr. Michael D. Waters of the Environmental Protection Agency and C. Christine Cox of Northrop Services, Inc., for the cadmium analyses on the liver samples; Joy A. Cavagnaro and Randale C. Sechrest for their participation in the aminopyrine demethylase and aniline hydroxylase assays; Dr. Edward J. Cafruny of Sterling-Winthrop Research Institute for generously supplying the hexobarbital sodium; and Susan P. Kelly and Linda K. Byrd for assistance in the preparation of the manuscript.
- Copyright © 1977 by Academic Press, Inc.
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