Early changes in the tissue distribution of cadmium after oral but not intravenous cadmium exposure.
The kinetics of 109Cd distribution in tissues of male and female mice were measured at intervals of 5 min to 15 days after oral (100 micrograms Cd/kg; by gavage) or intravenous (1 micrograms Cd/kg; i.v.) administration of 109CdCl2. Unexpectedly, the ratio of 109Cd in liver to that in kidneys was greater than or equal to 10 within 1 h after administration by either route. However, after 4 h, route-dependent differences in distribution between liver and kidney became apparent. In mice receiving oral cadmium, the liver:kidney 109Cd ratio decreased with time to approximately 4 at 72 h after gavage. In contrast, in mice receiving IV cadmium, the liver:kidney 109Cd ratio remained high and relatively constant during the same time period. The time-dependent decrease in the liver:kidney 109Cd ratio after oral cadmium administration was caused by a 4-5-fold increase in cadmium content of the kidney that occurred between 30 min and 72 h after oral but not i.v. administration. During this time, there was no change in cadmium distribution in subcellular fractions of either liver or kidney. These results could be explained by the existence of 2 separate pathways for cadmium deposition after oral exposure. Early after exposure, cadmium may leave the intestine, bind to serum albumins or other high molecular weight proteins, and accumulate primarily in liver, as is also observed after IV cadmium administration. With time, cadmium may leave the intestinal mucosa bound to metallothionein and deposit primarily in the kidney. The different pathways of deposition after oral vs. i.v. exposure may in part explain why acute parenteral cadmium exposure causes liver toxicity, but chronic oral exposure causes renal toxicity.
Jonah
M M
MM
Biological, Environmental, and Medical Research Division, Argonne National Laboratory, IL 60439.
Bhattacharyya
M H
MH
D000284:Administration, Oral; D000818:Animals; D001842:Bone and Bones / Q000378:metabolism; D002104:Cadmium / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002106:Cadmium Radioisotopes; D003600:Cytosol / Q000378:metabolism; D005260:Female; D007275:Injections, Intravenous; D007408:Intestinal Absorption; D007668:Kidney / Q000378:metabolism* / Q000648:ultrastructure; D007700:Kinetics; D008099:Liver / Q000378:metabolism* / Q000648:ultrastructure; D008297:Male; D051379:Mice; D014018:Tissue Distribution
D002106:Cadmium Radioisotopes; D002104:Cadmium