The toxicity of cadmium, zinc and molybdenum and their effects on copper metabolism

Abstract

'979 changes in Cu metabolism which occur when intakes of Zn, Cd or molybdenum are increased. Effects of Zn on Cu metabolism Although Zn is not generally regarded as a very toxic metal (Ott et al. 1966), signs of Cu deficiency can develop in rats if their diet contains about 5000 mg Zn/kg (e.g. Grant-Frost & Underwood, 1958). Because of the large amounts of Zn required to produce this effect it appeared at one stage that Zn toxicity was of limited biological importance. However, there is increasing evidence that this effect of Zn could be of some significance in both medicine and animal production. Oral administration of large amounts of Zn for the treatment of coeliac disease (Porter et al. 1977) and sickle cell anaemia (Prasad et al. 1978) has caused hypocupraemia and neutropenia in humans. At the other extreme, oral Zn has been used to reduce tissue accumulation of Cu and improve the clinical condition of patients with Wilson's disease, which is a form of Cu poisoning of genetic origin (Hoogenraad et ul. 1978). Similarly, dietary supplementation with Zn can afford protection against the development of Cu toxicosis in sheep, by reducing liver Cu concentrations (Bremner et ul. 1976). It is also possible that Zn-induced disturbances in Cu metabolism could be of importance in cases of environmental exposure of grazing animals to Zn. Herbage Zn concentrations in the vicinity of certain industrial plants can range from 160-3000 mg Zdkg, depending on the season and distance from the source of the Zn-emission (Mills & Dalgarno, 1972). Although these concentrations are less than those generally found necessary to produce Cu deficiency in rats, the studies of H i l l & Matrone (1970) show that the susceptibility of these animals to Zn is much greater if they are fed a low-Cu diet. Dietary Zn contents of only 200-400 mg/kg will then induce clinical signs of Cu deficiency. It is evident, therefore, that careful attention should be paid to the control of the Cu intake of animals in assessing the hazard associated with environmental exposure to Zn and other metals. In recent investigations of this topic at this Institute, the dietary Cu intake has deliberately been set at a level which was only just sufficient to meet the estimated requirement for this metal. Preliminary studies on rats showed that plasma caeruloplasmin activity could then be reduced by 40% in rats fed diets with only 300 mg Zdkg (Campbell & M i l l s , 1974). Increasing the Zn intake to 1000 mg/kg further decreased the activity of this Cu-containing enzyme and in addition reduced growth rate, affected skeletal development and decreased Cu concentrations in both liver and kidney. All these changes are indicative of Cu deficiency. A severe Cu deficiency could also be induced in pregnant ewes by feedmg them a diet with 750 mg Zdkg (Campbell & Mills, 1979). This was associated with a large reduction in growth rate and food intake. Moreover, the abortion rate was extremely high and the viability of the lambs which were alive at birth was low. The susceptibility of pregnant ewes to Zn toxicosis appears, therefore, to be much greater than that of growing or adult male sheep, which can tolerate Zn intakes of at https