Research advances defining how zinc is transported into and out of cells and organelles have increased exponentially within the past five years. Research has progressed through application of molecular techniques including genomic analysis, cell transfection, RNA interference, kinetic analysis of ion transport, and application of cell and animal models including knockout mice. The knowledge base has increased for most of 10 members of the ZnT family and 14 members of the Zrt-, Irt-like protein (ZIP) family. Relative to the handling of dietary zinc is the involvement of ZnT1, ZIP4, and ZIP5 in intestinal zinc transport, involvement of ZIP10 and ZnT1 in renal zinc reabsorption, and the roles of ZIP5, ZnT2, and ZnT1 in pancreatic release of endogenous zinc. These events are major factors in regulation of zinc homeostasis. Other salient findings are the involvement of ZnT2 in lactation, ZIP14 in the hypozincemia of inflammation, ZIP6, ZIP7, and ZIP10 in metastatic breast cancer, and ZnT8 in insulin processing...

Mammalian Zinc Transporters: Nutritional and Physiologic Regulation

Oxidative Stress as a Mechanism of Chronic Cadmium-Induced Hepatotoxicity and Renal Toxicity and Protection by Antioxidants☆☆☆★

Increased dietary cadmium absorption in mice and human subjects with iron deficiency

In this study we used the Forum of European Geological Surveys geochemical baseline data to examine the distribution of cadmium (Cd) in Europe, with a particular reference to the international soil and water guideline values. The highest cadmium levels were found to occur in topsoil and to follow closely the distribution of P2O5, suggesting that the contamination was from the use of rock phosphate fertilizer in intensive arable agriculture. In terms of human health impacts, food (up to several hundred μg/day) was found as the only major route of exposure to Cd for the non-smoking general population. It appeared that low levels of chronic exposure to Cd resulted in completely different human health impacts than those high levels that had caused the ‘itai–itai’ disease. Some correlations were suggested between cadmium levels and the age-adjusted prostate or breast cancer rates distributed in the European countries under study.

Cadmium levels in Europe: implications for human health

Principles and recent developments in chelation treatment of metal intoxication.

Radioactive cadmium (109Cd) and zinc (65Zn) were injected subcutaneously into pregnant rats. More cadmium than zinc was found in the placentae. After birth, newborns showed detectable 109Cd only in liver, gastrointestinal tract, and in the brain tissue. Zinc 65 was present in all newborns’ tissues. During lactation, highest output of 65Zn was in colostrum and, on subsequent days, 65Zn in milk declined rapidly. Cadmium 109 in milk was present in low concentration throughout the lactation period. Rats injected with 109Cd and 65Zn after parturition excreted these isotopes in milk in a similiar pattern. Newborns nursed on radioactive milk showed rapid absorption of 65Zn, whereas 109Cd accumulated primarily in the intestinal tract; a lesser quantity of 109Cd was deposited in the liver. In other organs, only 65Zn was found. The lactating mammary gland contained more 109Cd than 65Zn; after lactation, 65Zn was depleted, whereas 109Cd remained in mammary tissue.

Cadmium and Zinc in Pregnancy and Lactation

Rats and mice were injected subcutaneousty with cadmium chloride Cd 109 and zinc chloride Zn 65 Both isotopes concentrated primarily in liver and kidneys Tissue subcellular fractionation showed 70% to 80% 109Cd and 65Zn associated with cytoplasmic soluble fraction Soluble fraction gel filtration revealed most 109Cd was bound to proteins of 11,000 to 12,000 molecular weight; 65Zn was associated mainly with larger sized molecules In rats, two weeks following isotope dose, depletion of 65Zn from cytoplasmic macromolecules was demonstrated; 109Cd remained fixed to cadmium-binding proteins (Cd-BP) By ion-exchange chromatography, Cd-BP was resolved into major components Similar components were separated from human kidney Cd-BP Presence of Cd-BP was noted in humans and monkey liver tissues It is suggested that mammalian organism intracellular Cd-BP apparently acts as biochemical mechanism for sequestration of toxic Cd2+ ions

Cadmium and zinc binding in mammalian liver and kidneys.

In rat plasma, 109Cd was mainly associated with α-globulin fraction and 65Zn was bound to and β-globulins. Subcutaneously injected cadmium chloride Cd 109 and zinc chloride Zn 65 resulted in rapid clearance of 109Cd from blood plasma, as compared to 65Zn. Blood cells accumulated 65Zn more rapidity than 109Cd. Greatest uptakes of 109Cd per unit weight of tissue were by liver, kidneys, and pancreas, but that of 65Zn was by the pancreas. From all tissues, 65Zn was depleted eventually. In the first six hours after isotope dose, testis tissue concentrated more 109Cd than 65Zn. In testes, 65Zn-influx continued for 168 hours, without further 109Cd increase. Both isotopes were excreted predominantly via intestinal tract. Fecal and urinary excretion of 109Cd and 65Zn was accelerated by 2,3-dimercapto-1-propanol Results Indicate 109Cd follows metabolic pathways different from those of 65Zn.

Biological differences in cadmium and zinc turnover.

Distribution of subcutaneously injected cadmium 109 (109Cd) was studied in mature rats over a period of 14 days. Tthe isotope was primarily deposited in the kidneys, liver, and pancreas. Within four hours after injection, cadmium appeared in the wall and in the contents of the small intestine. In the colon and in its contents, the concentration of the isotope increased gradually over a period of 24 hours. Cadmium content in the intestinal tract decreased progressively between 30 and 336 hours after injection. The stomach wall concentrated and retained 109Cd, and only traces of the isotope appeared in the contents of the stomach. From the blood plasma, cadmium disappeared rapidly, whereas the blood cells showed an increase in cadmium concentration between 24 and 336 hours after injection.

Turnover of Cadmium 109 in Rats

Distribution of subcutaneously injected cadmium 109 (109Cd) and zinc 65 (65Zn) was studied in mature male mice of four different inbred strains. Mice of CBA/J and DBA/1J strains, which are known to be susceptible to cadmium-induced testicular necrobiosis, exhibited a greater uptake of 109Cd by the testes than cadmium-resistant strains C57BL/6J and BALB/cJ. The ratio of 109Cd/65Zn in the testes of cadmium-sensitive strains was several times higher than in the testes of cadmium-resistant strains. In all animals, the liver and the kidney tissue concentrated more cadmium than zinc. In other tissues, the uptake of zinc predominated that of cadmium.

Ojars J. Lucis Md

Papers

Cadmium and Zinc in Pregnancy and Lactation

Cadmium and zinc binding in mammalian liver and kidneys.

Biological differences in cadmium and zinc turnover.

Turnover of Cadmium 109 in Rats

Distribution of cadmium 109 and zinc 65 in mice of inbred strains.