Cellular localization of metallothionein (MT) in placenta may provide information on its function as a metal binding protein. Rabbit antibodies to rat liver MT cross-reacted with human MT and were used to localize MT in human term placenta by avidin-biotin peroxidase technique. Serial sections (5 microns) were cut from paraffin-embedded placentae obtained at term from five normal women and incubated with rabbit antibodies to MT. Normal rabbit serum was used as a negative control. The slides were incubated with biotinylated swine anti-rabbit IgG (linking antibody) then with avidin-biotin horseradish peroxidase complex and developed with diaminobenzidine in hydrogen peroxide (0.03 per cent) substrate. The optimum staining of MT was obtained at a 1:800 antibody dilution. MT was identified in fetal amniotic cells, syncytial trophoblasts and villous interstitial cells, and in maternal decidual cells. The presence of MT at specific cellular sites suggests that it may regulate the transplacental transport of metals such as zinc, copper and cadmium. Since the level of cadmium is lower and that of zinc and copper higher in fetal than in maternal blood, this may suggest that placental MT may restrict cadmium while enhancing zinc and copper transport.

Amniotic Fluid↗

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The work-relatedness of renal disease.

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Analgesics↗

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Gastrointestinal absorption and organ distribution of oral cadmium chloride and cadmium-metallothionein in mice.

Body retention and tissue distribution of Cd from oral 109CdCl2 and 109Cd-metallothionein were studied in C57BL/6J mice given identical doses (60 microgram Cd and 2 muCi 109Cd). Measurement of 109Cd radioactivity in mice showed identical absorption but differences in tissue distribution of Cd from the two forms. A significantly greater deposition of Cd was observed in the kidney of mice fed Cd-metallothionein than in the CdCl2 group where a major portion of Cd was deposited in the liver. Most of the radioactive Cd in the renal and hepatic tissue and in the duodenum was bound to metallothionein 24 h after oral Cd-metallothionein, whereas only 30 and 38% of the cadmium in liver and kidney supernatants, respectively, were bound to metallothionein after oral CdCl2. These results suggest that the dietary form of Cd may influence the renal deposition of Cd.

Animals↗

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Renal effects of repeated administration of calcium disodium ethylenediaminetetraacetate during excessive exposure to lead in rats.

The renal effects of repeated administration of EDTA were studied in rats given 0.5% lead as lead acetate in drinking water for 24 weeks. Repeated treatment of lead toxic rats with EDTA during continuous exposure to lead reduced blood lead levels and brain and bone lead but not to a statistically significant level (p greater than 0.05). Liver lead concentration in the EDTA treated, lead exposed rats changed only slightly upward, but kidney lead levels decreased greatly when compared to lead exposed, non-EDTA treated rats, (group IV vs. group III), (p less than 0.05). Light and electron microscopy of kidneys of lead treated rats showed evidence of an early interstitial nephropathy characterized by peritubular fibrosis and variation in size of tubular cells. Nuclei of renal tubular cells of lead exposed rats had inclusion bodies, but these were not present in lead exposed, EDTA treated rats. The present study suggests that repeated treatment of rats with EDTA during continuous exposure to lead reduces renal lead concentration but does not significantly influence the progression of lead induced nephropathy.

Animals↗

PubMedDate not supplied

Role of metallothioneins in disease.

Metallothioneins are small proteins (6,000 to 10,000 mw) with similar amino acid compositions, high content of sulfhydryl amino acids and no aromatic amino acids. Emax at 250 nm is due to cadmium mercaptide bond. Synthesis is induced by a number of metals including zinc, cadmium, mercury, copper, bismuth, gold and silver. These proteins function as a mechanism of intracellular storage of some essential metals such as zinc and copper. Binding of potentially toxic metals like cadmium may be protective; but with saturation of protein by metal, toxicity may occur. Excessive cadmium-thionein may have a role in the pathogenesis of cadmium induced kidney disease. A more sensitive method for detection adn measurement of this protein will greatly enhance future studies, particularly the potential for clinical application.

Animals↗