Potential interactions of ionophore drugs with divalent cations and their function in the animal body

The ionophoretic antibiotics, monensin and lasalocid, bind numerous mono- and divalent cations, primarily in dimeric complexes that facilitate the passage of metal ions through hydrophobic lipid membranes. Ionophores vary in their affinity for metal ions. Similarly, transport rates of the resulting complexes depend in part upon the affinity constant of the drug ion-binding interaction, and in part, upon local environmental and physical factors. The normal uptake, transport and use of divalent minerals in the animal body is accomplished via numerous endogenous "ionophore" transport routes. We studied the possibility that exogenous ionophores such as monensin and lasalocid might alter normal intestinal uptake of divalent metal ions. In the first experiment, chickens were fed either monensin or lasalocid; 45Ca, 59Fe or 64Cu was individually instilled into an exteriorized isolated loop of the duodenum and absorption allowed for 1 h. Radioactivity was measured in the duodenal mucosa. Compared with controls, 59Fe and 64Cu were lower in tissues from animals given monensin, but higher in animals given lasalocid. 45Ca was lowered in gut mucosa by both drugs. In the second experiment, liver Cu, Fe and Zn were measured in chickens and sheep fed diets containing monensin or lasalocid. Small differences in basal tissue levels of ions were observed in both sheep and chickens fed the ionophoretic drugs. Drenching sheep with 100 mg X animal-1 X d-1 Cu2+ as CuSO4 resulted in enhanced Cu accumulation in all animals, with the largest accumulation measured in those fed monensin. These preliminary data suggest that adding monensin and lasalocid to diets may change the bioavailability, gut uptake and tissue deposition of divalent minerals.(ABSTRACT TRUNCATED AT 250 WORDS)