Abstract
Cadmium was administered into male rats in drinking water as cadmium chloride at a concentration equivalent to 250 ppm of cadmium for 2 and 8 weeks. The cadmium concentration in the liver microsomes was 0.85±0.11⧎g/g (wet wt) and in the supernatant 29.6±1.1μg/g and in the renal microsomes 1.30±0.30μg/g (w.wt) and in the supernatant 24.4+3.2μg/g after 8 weeks. In the intestinal postmitochondrial supernatant fraction the cadmium concentration was 14.2±1.0μg/g (wet wt) after 8 weeks administration. There was a slight increase in the hepatic cytochrome P-450 level, no changes in the hepaticp-nitroanisoleO-demethylase and NADPH cytochrome c reductase activities and aclearcut induction in the hepatic aryl hydrocarbon hydroxylase activity after 8 weeks cadmium exposure. Renal activities followed mainly those of the liver. No changes were found in the hepatic UDPglucuronosyltransferase activity and a slight activation was present in the renal activity. The intestinal activities were markedly depressed after cadmium exposure. The results suggest that cadmium administration changes the drug biotransformation rates differently in various tissues.
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Brancato, D. J., A. L. Picchioni, and I. Chin: Cadmium levels in hair and other tissues during continuous cadmium intake. J. Toxicol. Environ. Health2, 351 (1976).
Bremner, J.: Heavy metal toxicities. Q. Rev. Biophys.7, 75(1974).
Calop, J., M.-E. Burchkart, and R. Fontanges: Etude de l'influence des éléments traces sur l'hydroxylation du benzo(a)pyréne. Eur. J. Toxicol.9, 271(1976).
Colucci, A. V., D. Winge, and J. Krasno: Cadmium accumulation in rat liver. Arch-Environ. Health30, 153(1975).
Der, R., Z. Fahim, M. Yousef, and M. Fahim: Environmental interaction of lead and cadmium on reproduction and metabolism of male rats. Res. Commun. in Chem. Path. Pharmacol.14, 689(1976).
Fassett, D. W.: Cadmium: Biological effects and occurance in the environment. Ann. Rev. Pharmacol.15, 425(1975).
Fishbein, L.: Environmental metallic carcinogens: An overview of exposure levels. J. Toxicol. Environ. Health2, 77(1976).
Gornall, A. G., C. J. Bardawill, and M. M. David: Determinations of serum proteins by means of the biuret reaction. J. Biol.Chem.177, 751(1949).
Hänninen, O.: On the metabolic regulation in the glucuronic acid pathway in the rat tissues. Ann. Acad. Sci. Fenn.A2, (No 142), 1 (1968).
Isselbacher, K. J.: Enzymatic mechanisms of hormone metabolism. II. Mechanism of hormonal glucuronide formation. Recent Progr. in Horm. Res.12, 134(1956).
Leber, A. P., and T. S. Miya: A Mechanism for cadmium- and zinc-induced tolerance to cadmium toxicity: Involvement of metallothionein. Toxicol. Appl. Pharmacol.37, 403(1976).
Nebert, D. W., and H. V. Gelboin: Substrate-inducible microsomal aryl hydrocarbon hydroxylase in mammalian cell culture. J. Biol. Chem.234, 6242(1968).
Netter, K. J.: Eine Methode zur direkten Messung derO-demethylierung Lebermikrosomen und ihre Anwendung auf die Mikrosomen hemmwirkung von SKF 525-A. Naunyn-Schmiedeberg's Arch. Pharmacol.238, 292 (1960).
Omura, T., and R. Sato: The carbon-monoxide binding pigment of liver microsomes. II. Solubilization, purification and properties. J. Biol. Chem.239, 2379(1964).
Phillips, A. H., and R. G. Langdon: Hepatic triphosphopyridine nucleotide-cytochrome c reductase: Isolation, characterization and kinetic studies. J. Biol. Chem.237, 2652(1962).
Shaikh, Z., and J. C. Smith: The biosynthesis of metallothionein in rat liver and kidney after administration of cadmium. Chem.-Biol. Interactions15, 327(1976).
Squibb, K. S., J. Cousins, B. L. Silbon, and S. Levin: Liver and intestinal metallothionein: Function in acute cadmium toxicity. Exp. Molec. Path.25, 163(1976).
Stoll, R. E., J. F. White, T. S. Miya, and W. F. Bousquet: Effects of cadmium on nucleic acid and protein synthesis in rat liver. Toxicol. Appl. Pharmacol.37, 61(1976).
Stonard, M. D., and M. Webb: Influence of dietary cadmium on the distribution of the essential metals copper, zinc and iron in tissues of the rat. Chem.-Biol. Interactions15, 349(1976).
Tati, M., Y. Katagiri, and M. Kawai: Urinary and fecal excretion of cadmium in normal Japanese: An approach to non-toxic levels of cadmium. In G. F. Nordberg (Ed.): Effects and Dose-Response Relationships of Toxic Metals, p. 331. Amsterdam: Elsevier (1976).
Unger, M., and J. Clausen: Liver cytochrome P-450 activity after intraperitoneal administration of cadmium salts in the mouse. Environ. Physiol. Biochem.3, 236(1973).
Vainio, H.: Drug hydroxylation and glucuronidation in liver microsomes of phenobarbital treated rats. Xenobiotica3, 715(1973).
Valberg, L. S., J. Sorbie, and L. Hamilton: Gastrointestinal metabolism of cadmium in experimental iron dificiency. Amer. J. Physiol.231, 462(1976).
Wagstaff, D. D.: Stimulation of liver detoxication enzymes by dietary cadmium acetate. Bull. Environ. Contam. Toxicol.10, 328(1973).
Wattenberg, L. W., J. L. Leong, and P. J. Strand: Benzpyrene hydroxylase activity in the gastrointestinal tract. Cancer Res.22, 1120(1962).
Webb, M., and L. Magos: Cadmium-thionein and the protection by cadmium against the nephrotoxicity of mercury. Chem.-Biol. Interactions14, 357(1976).
Yoshida, T., Y. Ito, and Y. Suzuki: Inhibition of hepatic drug metabolizing enzymes by cadmium in mice. Bull. Environ. Contam. Toxicol.15, 402(1976).
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Hietanen, E. Cadmium-induced tissue specific changes in drug biotransformation rates in rats. Arch. Environ. Contam. Toxicol. 7, 291–300 (1978). https://doi.org/10.1007/BF02332057
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DOI: https://doi.org/10.1007/BF02332057