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Molecular Pharmacology, Vol 13, 759-765, Copyright © 1977 by the American Society for Pharmacology and Experimental Therapeutics

Effects of Cadmium on Microsomal Hemoproteins and Heme Oxygenase in Rat Liver

HARVEY C. KRASNY 1 and DAVID J. HOLBROOK JR. 1

1 Wellcome Research Laboratories, Research Triangle Park, North Carolina 27709, and Department of Biochemistry, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27514

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]dgr-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+.

Note:
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.

Submitted on September 27, 1976
Accepted on March 21, 1977




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