Kinetic analysis of zinc metabolism in humans after simultaneous administration of 65Zn and 70Zn

Zinc kinetics were studied and compared after oral simultaneous administration of two tracers, radioactive (65Zn) and stable (70Zn) isotope, to four normal human volunteers. Both tracers and zinc concentration were measured in plasma, red blood cells (RBC), urine, and feces for up to 78 days. Radioactive zinc was also measured by external counting over whole body, liver, and thigh. Data from each individual were analyzed using a compartmental model for zinc metabolism. Values calculated for absorption, fractional zinc excretion in urine, exchange with RBC, and secretion into gut using 70Zn data did not differ from values calculated using 65Zn data. Results show that human zinc metabolism can be investigated using stable isotopes as tracers to determine parameters of whole body zinc metabolism, including zinc absorption, excretion, and secretion.

Induction of hepatic metallothionein by feeding zinc to rats of depleted zinc status

Induction of hepatic metallothionein was investigated in zinc-depleted rats after a single feeding (via stomach tube) of a complete diet with or without supplemental zinc. Subsequent to a maximum elevation in serum zinc (3.25 micrograms/ml) at 3 h, the rate of metallothionein synthesis increased 4.5-fold by 10 h after feeding. Changes in the rate of metallothionein synthesis coincided with similar changes in the level of translatable mRNA coding for metallothionein. Accumulation in liver of Zn2+ as metallothionein rose to a maximum by 12 h after diet administration and thereafter remained constant. Radioactive zinc (65Zn) included in the diet rapidly associated with newly formed metallothionein. Unlike Zn2+, 65Zn exhibited marked fluctuations within the 24-h period following feeding, indicating that zinc associated with metallothionein may be capable of exchange and/or dissociation. Changes in total liver 65Zn were accompanied by concomitant changes in metallothionein-bound 65Zn. This study has related (temporally) the metabolism of dietary zinc to the induction, apparently via transcription of mRNA, of hepatic metallothionein.

Role of prostaglandin E2 in zinc absorption in the rat.

The supernatant of cytoplasmic extract of rat small intestine was mixed with 65Zn and subjected to Sephadex G-75 column chromatography. The activity of 65Zn was detected in four peaks with estimated 800, 10,000, 50,000-75,000 mol wt, and larger than 100,000 daltons. The zinc-binding ligand from the 800 mol wt peak was prostaglandin or prostaglandin-like as indicated by ultra-violet absorption spectrum, by absorption spectrum shift in alcoholic potassium hydroxide, by its effects on pulmonary vascular resistance, and by radioimmunoassay. Addition of prostaglandin E2 or prostaglandin extracted from rat small intestine with ethyl acetate into the lumen of intestinal sacs resulted in a two to threefold increase in the activity of 65Zn in the external medium after 15-20 min incubation. The absorption and tissue distribution of orally administered 65Zn were decreased by 60% in indomethacin-treated rats and increased 70% when ethyl acetate-extracted prostaglandin and radioactive zinc were given simultaneously. These data suggest that prostaglandin not only binds zinc, but also facilitates its transport across the intestinal mucosa.