Tissue accumulation of cadmium following oral administration to metallothionein-null mice.
To verify the roles of intestinal metallothionein (MT) as a barrier against ingested cadmium (Cd) and as a transporter of mucosal Cd to the kidneys, the distribution of orally administered Cd was compared between normal and MT-I and -II knock-out (MT-null) mice. Following single administration of a low dose of Cd (0.1 mg/kg), hepatic Cd levels and the sum of total Cd in the liver and kidney (K + L) were significantly less in the controls than in MT-null mice. The ratio of Cd in the kidney to the liver (K/L) was significantly lower in the MT-null mice. On the other hand, at a high Cd dose (2.0 mg/kg), K + L and K/L were not significantly different between the two groups. However, following oral pretreatment with zinc (Zn) to the high dose control mice, K + L significantly decreased and K/L significantly increased. No such effects of Zn pretreatment were observed in MT-null mice. Similar differences in K + L and K/L were also observed between the control and MT-null mice groups following the Zn pretreatment. Repeated administration of Cd for 4 weeks resulted in significantly larger K/L distribution in control mice over null mice. These results suggest that MT in the intestinal mucosa functions both as a protective barrier against Cd absorption and as an extracellular transporter of Cd to the kidney.
Kimura
T
T
Toxicology Laboratory, Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Japan.
Itoh
N
N
Min
K S
KS
Fujita
I
I
Muto
N
N
Tanaka
K
K
D000284:Administration, Oral; D000818:Animals; D002104:Cadmium / Q000378:metabolism*; D019256:Cadmium Chloride / Q000008:administration & dosage*; D017353:Gene Deletion; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008668:Metallothionein / Q000172:deficiency / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D014018:Tissue Distribution; D015032:Zinc / Q000494:pharmacology
D002104:Cadmium; D008668:Metallothionein; D015032:Zinc; D019256:Cadmium Chloride