Systemic Dispositions of Molybdenum and Copper after Tetrathiomolybdate Injection in LEC Rats

Abstract

Mutant Long-Evans rats with a cinnamon coat-color (LEC rats) have been established as an animal model for Wilson disease, a genetic disorder of copper (Cu) metabolism. Systemic disposition of molybdenum (Mo) and altered distributions of Cu were compared in eight organs between LEC rats and Wistar rats (normal) at different times after a single intraperitoneal injection of tetrathiomolybdate (TTM) for chelation therapy. Excretion through urine and feces was also examined. Hepatic disposition of Mo was dramatically increased in LEC rats, suggesting that the interaction of TTM with Cu results in enhanced uptake of Mo. Concentrations of Mo and Cu decreased in the liver of LEC rats over time, whereas those in the spleen increased. Although the concentration of Mo taken up by the kidney decreased over time after an initial increase in both rats, Cu concentration increased over time. Cu was not redistributed to the brain. Excretion of Mo through urine was decreased and that into feces was increased in LEC rats compared with those in Wistar rats. These results indicate that TTM is taken up by the liver depending on the Cu content, and the Cu and Mo removed from the liver are mostly excreted through feces. Redistribution of Cu was observed in the spleen and kidneys, but not in the brain.