Profiles of 67Cu in blood, bile, urine and faeces from 67Cu-primed lambs: effect of 99Mo-labelled tetrathiomolybdate on the metabolism of recently stored tissue 67Cu

Abstract

1. The relative importance of excretory routes in the removal of recently stored 67Cu following tetrathiomolybdate (TTM) administration was studied. Lambs fed on either 5 mg Cu/kg dry matter (DM) or 35 mg Cu/kg DM, were primed intravenously (iv) with 67Cu and challenged 27 h later with 99Mo-labelled TTM given either iv or intraduodenally (id). The profiles of 67Cu and 99Mo and of Cu and Mo in blood, bile, urine and faeces were measured.2. Level of dietary Cu and route of administration of 99Mo-TTM affected the amplitude of blood, bile and urine profiles of 67Cu and stable Cu, but not the pattern of the responses observed.3. The present study describes for the first time increased excretion of endogenous 67Cu through gastrointestinal secretions other than bile due to TTM administration.4. Administration of TTM resulted in the immediate release of 67Cu from storage compartments in the body into the blood circulation. Changes in stable Cu levels in blood, bile, urine and faeces, and gut and systemic effects were evident. Biliary and urinary Cu excretion due to TTM was rapid and maximal within 24 h of injection.5. Administration of 67Cu iv resulted in the immediate excretion of 67Cu in bile in a pulsatile, constant pattern. A similar pattern of 67Cu excretion into bile in synchrony with that of 99Mo was observed after 99Mo-labelled TTM administration.6. The similar pattern of biliary 67Cu excretion observed after injection of 67Cu and after injection of 99Mo-labelled TTM 27 h later is discussed in relation to the times required to process the Cu through different hepatic pathways for excretion in bile.