Metallothionein-null and wild-type mice show similar cadmium absorption and tissue distribution following oral cadmium administration.
Cadmium (Cd) is an environmental pollutant and is toxic to many tissues. Food is the primary source of Cd exposure for the general population. Metallothionein (MT), a cysteine-rich, Cd-binding protein, plays an important role in Cd detoxication. However, the role of MT in Cd absorption and distribution is still controversial. For example, some reports assert that MT in the intestine decreases Cd absorption and increases its distribution to the kidney, relative to the liver. Therefore, to further clarify the role of MT in Cd absorption and tissue distribution, MT-I/II knockout (MT-null) mice and their parental background wild-type mice were given a single dose of (109)Cd (1-300 micromol/kg po or 0.1-30 micromol/kg iv). Cd content in 15 organs was determined 4 h after Cd administration by gamma scintillation spectrometry. Approximately 60% of the Cd administered iv was retained in liver, and about 5% was retained in kidney in both MT-null and wild-type mice. The distribution of iv administered Cd was independent of dose. In contrast, when administered po, approximately 0.15% of the lowest dose (1 micromol/kg) and 0.75% of the highest dose (300 micromol/kg) was detected in the liver of both MT-null and wild-type mice. Similarly in kidney, approximately 0.05% of the dose was detected after the lowest dose and about 0.15% after the higher doses in both MT-null and wild-type mice. In summary, this study demonstrates that the absorption and initial distribution of orally administered Cd is dose dependent but is not influenced by MT.
Liu
Y
Y
Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, KS 66160-7417, USA.
Liu
J
J
Klaassen
C D
CD
D000284:Administration, Oral; D000818:Animals; D002104:Cadmium / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000493:pharmacokinetics*; D005260:Female; D006720:Homozygote; D007275:Injections, Intravenous; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D011247:Pregnancy; D013051:Spectrometry, Gamma; D014018:Tissue Distribution
D004785:Environmental Pollutants; D002104:Cadmium; D008668:Metallothionein