Kinetics of Cd2+ in plasma, liver and kidneys after single intravenous injection of Cd-metallothionein-II.
To explore the kinetics of Cd2+ in the body, rats received a single intravenous injection of CdCl2 or Cd-saturated metallothionein-II at 0.3 mg Cd/kg body weight. Cd2+ in the two agents was biexponentially eliminated from plasma: rapidly in the first 5 min, and gradually later. Compared with CdCl2, Cd-saturated metallothionein-II showed lower Cd2+ concentrations in plasma during the first 30 min; larger values for parameters concerning distribution of Cd2+, its total body clearance and half-life time in the beta phase. Cd2+ uptake in the liver was higher with CdCl2, and, conversely, in the kidneys it was higher with Cd-saturated metallothionein-II. In Cd-saturated metallothionein-II, the renal content of Cd2+ reached a maximum (8 micrograms Cd2+/g tissue) on day 1, gradually decreasing thereafter; there was a higher area under the Cd2+ content-time curve, and a lower mean residence time of Cd2+; the kidneys showed severe necrosis and defluxion of proximal tubular cells at days 1 and 5, although there were regenerative and reversion signs on day 5. These findings suggested that, in the case of Cd-saturated metallothionein-II, Cd2+ being taken into the cells of proximal tubules was excluded predominantly due to cellular death and the resultant defluxion.
Department of Toxicology and Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Higashi-Nippon-Gakuen University, Hokkaido, Japan.
J
J
Sudo
T
T
Hayashi
J
J
Terui
M
M
Soyama
M
M
Fukata
K
K
Kakuno
D000818:Animals; D002104:Cadmium / Q000097:blood / Q000493:pharmacokinetics* / Q000633:toxicity; D007275:Injections, Intravenous; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008668:Metallothionein / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008954:Models, Biological; D051381:Rats; D017207:Rats, Sprague-Dawley
C004203:cadmium-binding protein; D002104:Cadmium; D008668:Metallothionein