Cadmium-induced tissue specific changes in drug biotransformation rates in rats.
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 microgram/g (wet wt) and in the supernatant 29.6 +/- 1.1 microgram/g and in the renal microsomes 1.30 +/- 0.30 microgram/g (w.wt) and in the supernatant 24.4 +/- 3.2 microgram/g after 8 weeks. In the intestinal postmitochondrial supernatant fraction the cadmium concentration was 14.2 +/- 1.0 microgram/g (wet wt) after 8 weeks administration. There was a slight increase in the hepatic cytochrome P-450 level, no changes in the hepatic p-nitroanisole O-demethylase and NADPH cytochrome c reductase activities and a clearcut 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.
D000818:Animals; D001711:Biotransformation; D001835:Body Weight / Q000187:drug effects; D002104:Cadmium / Q000378:metabolism / Q000494:pharmacology*; D004386:Duodenum / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008297:Male; D009929:Organ Size / Q000187:drug effects; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D051381:Rats; D013347:Subcellular Fractions / Q000201:enzymology / Q000378:metabolism
D004364:Pharmaceutical Preparations; D002104:Cadmium