Copper and molybdenum absorption by rats given ammonium tetrathiomolybdate

Previous studies have shown that the tetrathiomolybdate ion [MoS4(2-)] is a potent antagonist of Cu metabolism. Effects of orally administered MoS4(2-) on the absorption and tissue distribution of 64Cu in rats have now been investigated. Four or 12 mg Mo/kg diet, when given as MoS4(2-), strongly inhibited 64Cu absorption and modified the fate of absorbed Cu, decreasing hepatic and renal uptake but increasing plasma retention of 64Cu. These effects were not induced by equivalent dietary concentrations of Mo as MoO4(2-) or when S2- was given as CaS. Clinical and biochemical effects induced by orally administered MoS4(2-) were abolished by increasing dietary concentrations of Cu. Such treatment also inhibited the absorption and tissue retention of 99Mo derived from 99MoS4(2-). Intraperitoneal administration of Cu ameliorated clinical effects attributable to MoS4(2-) but neither inhibited 99Mo absorption nor the appearance of systemic defects in Cu metabolism. Since the absorption of MoS4(2-) (or its derivatives) from the gastrointestinal tract is inhibited by Cu, it is evident that the site of its action as an antagonist influencing either the absorption or the subsequent metabolic fate of Cu depends upon the ratio Cu/MoS4(2-) in the diet.