Search

A brief review of the literature indicates that nutritional deficiencies have been shown to increase the absorption and toxicity of orally ingested lead and cadmium. Results from recent studies indicates that low level oral ingestion of cadmium and lead perturbs the metabolism of zinc, copper, and iron and that these changes may be the earliest manifestation of the toxicity of lead and cadmium. The significance of these findings reveals itself in two ways: namely, that toxicologic investigations of lead and cadmium, whether experimental or clinical, must be based on a definitive consideration of the nutritional status of animals or people, and, secondly, that the preventive role of nutrition, especially that of trace metal intakes, must be taken seriously when establishing measures for reducing, eliminating, or combatting the toxic effects of widespread exposure to lead and cadmium in humans.

Lead-induced anemia in rats, which is of a microcytic, hypochromic type, has been shown to be a result of an interference with the metabolism of copper and iron. In this complex interaction, copper may be the target upon which ingested lead has its antagonistic effect on hematopoiesis. The depressions in hematocrit and hemoglobin levels resulting from exposure to lead may occur secondarily to the effects of a lead-induced copper deficiency on iron mobilization and utilization. The metabolic fault induced by lead is seen in a reduction of serum iron, elevation of serum iron binding capacity, and increase in liver iron, all manifestations of systemic effects related to an interference with copper metabolism. These results relate many of the characteristics of the lead-induced anemia to those found in the copper-deficiency anemia.

Both dietary iron and copper were inversely related to lead absorption as indicated by erythrocyte and kidney lead levels, dietary iron having the greatest effect. Kidney copper values were depressed when dietary iron was low, a condition which was worsened by lead. Lead tended to lower heart cytochrome c oxidase especially when dietary copper was low, but also when dietary copper and zinc were high. Lead interfered with hematopoiesis when dietary copper and/or iron were low, the effect being expecially severe when both essential nutrients were low. These results show the importance of copper and iron nutriture and metabolism as factors which reduce lead toxicity, and emphasize the necessity of considering nutritional status in evaluating lead toxicity.

Seven para-substituted [phenylglyoxal bis(4-methyl-3-thiosemicarbazone)]copper (II) chelates (12-18) have been designed, synthesized, and tested for their ability to inhibit the respiration of rat liver slices as a normal cell model and Ehrlich ascites cells as a tumor cell model. Relationships between chemical structure and respiratory inhibition are described on a quantitative basis using substituent contants (pi, Es, and sigmap) by computerized multiparameter regression analyses. The correlations indicate that changes in Es have the largest effect on liver slice toxicity of chelates while pi and sigmap account for most of the variation in toxicity to ascites cells. A comparative analysis strongly suggests that electron-donating substituents with greater water solubility should increase cytotoxicity to ascites cells at the expense of cytotoxicity to the rat liver cells. The predictions of the equations were checked by synthesizing and testing an additional derivative. The results strengthen the initial predictions.

Data are presented to show that ingestion of cadmium chloride by rats at low levels leads to alteration of zinc metabolism in the liver, even though the formation of metallothionein is not evident. A dose-response relationship between amount of cadmium ingested and degree of perturbation of zinc metabolism in liver was found. Oral cadmium was shown to cause emphysema and reduce pulmonary function in male rats; the effect was less severe or delayed in onset if dietary zinc concentration was high. Interference with copper and iron metabolism was shown to occur in rats given low levels of cadmium orally. Depression of copper and iron metabolism of the rat fetus was found to occur when dams received very low doses of cadmium during gestation, even though very little cadmium passed the placental barrier.

Weanling rats were fed a copper-deficient purified diet. The effects of varying the type of protein and supplements of copper and zinc on cardiovascular pathology and some biochemical parameters were investigated. It was found that cardiomyopathy developed in the copper-deficient groups. Milk powder caused significant exacerbation of this development relative to dietary casein or egg white. Angiopathy developed only when dietary zinc was 20 ppm. Dietary copper did not change this situation. Serum cholesterol was elevated when copper was low and casein or milk powder were the protein source. The data point to an interaction between type of protein and dietary copper or zinc in the pathogenesis of cardiovascular lesions.