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I R Record

Publications and source records attributed to I R Record.

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Interactions of cadmium and zinc in cultured rat embryos.

Rat embryos were cultured in serum taken from animals dosed with cadmium, or serum with cadmium added in vitro in the presence or absence of additional zinc. Embryos explanted at day ten and grown in serum taken from animals sooner than 4 h after dosing had a reduced DNA content after 24 h culture. In one-hour serum, the yolk sac had become thick and brittle. Zinc ameliorated the effects but had no stimulatory effect on post eight-hour serum when serum zinc levels were at their lowest. The hypothesis that cadmium induces a maternal zinc deficiency sufficient to cause teratogenic changes could not be sustained. Embryos explanted at nine days were much more susceptible to cadmium added in vitro than ten-day embryos. The principal anomaly, apart from a reduced DNA content, was a thickening of the yolk sac similar to that seen in embryos grown in serum taken from animals one hour after cadmium dosing. Addition of zinc to the medium prevented both of these effects. The suggestion is made that the cadmium-induced dysgenesis of the yolk sac precludes appropriate embryonic nutrition.

Animals↗

Inhibition of rat yolk sac pinocytosis by cadmium and its reversal by zinc.

The effect of cadmium on the in vitro pinocytic rate of 10- and 11-day-old rat yolk sacs grown on rat serum in culture was studied using the synthetic substrate 125I-labeled polyvinylpyrrolidone. In medium containing concentrations of added cadmium similar to those achieved in serum by intraperitoneal dosing of rats, the rate of pinocytosis in vitro was decreased by up to 55%. When zinc was included in the medium as well, the effect of cadmium was markedly reduced, and the rate of pinocytosis was restored to about normal. The results of this in vitro study suggest that cadmium can limit and supply of nutrients to the rat embryo in a nonspecific manner, and that elevated levels of zinc can restore the ability of the yolk sac to accumulate substances from the surrounding medium. Whereas cadmium may act as a teratogen at a number of sites, the demonstrated effect of this metal on the yolk sac provides a new insight into what could be a primary mode of action of cadmium on fetal development.

Animals↗

The effect of ethanol and acetaldehyde on DNA synthesis in growing cells and on fetal development in the rat.

Incorporation of 3H-thymidine into DNA was significantly diminished by treatment with ethanol and acetaldehyde in regenerating rat liver, rat cells in culture, and rat fetal tissues. Reduced incorporation was especially marked in the fetal central nervous system and was observed with both compounds at levels similar to those reported to occur in human alcoholics. The reduced incorporation of 3H-thymidine into fetal DNA, together with the increased fetal mortality observed in dams treated specifically with acetaldehyde during pregnancy, suggests that acetaldehyde is implicated in the mechanism of teratogenesis associated with the fetal alcohol syndrome.

Acetaldehyde↗

High plasma zinc levels following oral dosing in rats and the incorporation of 3H-thymidine into deoxyribonucleic acid in rat fetuses.

In fasted rats, a single oral dose of zinc, equivalent to the total daily zinc intake, caused plasma zinc levels to rise about five-fold 1.5 h after treatment. Higher values were obtained following higher dose levels. At maternal plasma zinc levels approximately 10-fold above normal, fetal viability was disturbed and incorporation of 3H-thymidine into DNA became impaired in fetal (20-d) rat brain and liver tissue.

Animals↗

Superoxide dismutase (EC 1.15.1.1), zinc status and ethanol consumption in maternal and foetal rat livers.

1. The activity of superoxide dismutase (EC 1.15.1.1) was not greatly affected by zinc deficiency in maternal or foetal (20 d) rat livers, although in the latter tissue it did appear to be slightly raised by Zn depletion when compared with pair-fed control animals. 2. Enzyme activity was significantly higher in livers from all foetuses after administration of aqueous ethanol at 100 or 200 ml/l to the dams during pregnancy. 3. Plasma Zn levels were significantly increased in Zn-deficient dams after ingestion of alcohol during pregnancy.

Animals↗

Lysosomal stability, superoxide dismutase and zinc deficiency in regenerating rat liver.

1. Lysosomal stability was slightly increased in regenerating livers from rats receiving a zinc-deficient (less than 0.5 mg/kg) diet for 10 d before surgery. 2. The activity of superoxide dismutase (EC 1.15.1.1) was significantly reduced in the same tissues. 3. The results do not support the view that increased lysosomal fragility represents a major biochemical consequence of nutritional Zn deficiency in animals.

Animals↗

Zinc, iron, vitamin E, and erythrocyte stability in the rat.

Previous studies have shown that deficiencies of zinc and vitamin E, as well as iron excess, contribute to peroxidative damage in several tissues in vivo. The present study reports on the sensitivity of red blood cells from young rats exposed to individual or concurrent imbalances of these three nutrients. For 21 d, rats were fed diets that were either deficient or replete in zinc and with or without excess iron or replete or deficient in vitamin E. When red blood cells from these rats were incubated in vitro, erythrocyte hemolysis, lipid peroxidation (assessed by MDA production), and hemoglobin degradation (assessed by alanine release), did not significantly increase unless vitamin E had been omitted from the diet. These results imply that either adequate tightly-bound zinc exists within the zinc-deficient cell to protect it from oxidative damage, or that other antioxidant defense mechanisms (including vitamin E) present within the plasma membrane and cytosol are sufficient to protect the cell from the otherwise damaging effects of zinc deficiency and/or iron excess.

Alanine↗