Endogenous Zinc Excretion Research Articles

Absorption, Distribution and Endogenous Excretion of Zinc by Rats Fed Various Dietary Levels of Inorganic Tin and Zinc

Three studies were designed to determine the effects of various levels of tin (<1, ∼100, ∼200, ∼500 and ∼2000 µg tin/g diet) and zinc (∼15, ∼30, ∼52 µg zinc/g diet) on the metabolism of zinc by growing rats. Retention of zinc in tibia, kidney, liver and plasma was decreased significantly when rats consumed ≥500 µg tin/g diet. Tibia zinc levels were also sensitive to lower levels of dietary tin, i.e., even 100 µg tin/g diet when rats were fed 51.8 µg zinc/g diet. Apparent absorption of zinc was significantly less when rats were fed ∼200 or ∼500 µg tin/g diet rather than a control diet containing 15.8 µg zinc/g diet and significantly less when rats were fed ∼500 µg tin/g diet rather than ∼200 µg tin/g diet with 29.7 µg zinc/g diet. The effect of dietary tin on fecal excretion of endogenous zinc and true absorption of zinc seemed to be dependent on the dose. Rats fed ∼2000 µg tin/g diet lost significantly more zinc of endogenous origin in the feces than control animals. A significant decrease in true absorption of zinc was observed among those rats fed ∼500 µg tin/g diet with 29.7 µg zinc/g diet. Increased consumption of zinc resulted in decreased apparent absorption of zinc, increased losses of endogenous zinc in the feces, and decreased true absorption of zinc.

A Model to Produce Pure Zinc Deficiency in Rats and Its Use to Demonstrate that Dietary Phytate Increases the Excretion of Endogenous Zinc

An early effect of zinc deficiency in rats is loss of appetite with consequent malnourishment. To obviate the need for pair-feeding, rats were fed liquid semipurified diets by gastric tube feeding. Rats tube fed a zinc-deficient diet at a daily rate of 90–110 g/kg thrived for 6–7 days and then rapidly became seriously ill. In contrast rats fed the deficient diet ad libitum stopped growing after 3 days but remained relatively healthy. Animals tube fed a zinc-replete diet or the deficient diet with subcutaneous injections of zinc grew normally and suffered no ill effects. Rats tube fed the deficient diet and supplemented parenterally with zinc excreted significantly more endogenous zinc into small intestinal luminal washings and into feces than unsupplemented rats. Sodium phytate, added to the tube feed in three groups of rats fed the deficient diet and supplemented daily with 0, 0.33 and 3.3 mg Zn/kg, significantly increased the zinc content of luminal washings in all three groups, increased fecal zinc excretion in two groups and lowered body zinc levels, estimated by femur zinc, in two groups. Tube feeding provides a means to study: 1) pure zinc deficiency without malnourishment of other nutrients; and 2) the excretion of endogenous zinc into the gastrointestinal tract.

Effect of Phytic Acid on the Absorption, Distribution, and Endogenous Excretion of Zinc in Rats

Zinc metabolism in male rats was studied by combining nutritional balance methods with an analysis of 65Zn kinetics. The rats, two groups of 84 each, were fed zinc-adequate diets (33 ppm Zn) with either 0 (basal) or 2% phytic acid added as sodium phytate. A fourth-order exponential function described the time-course of 65Zn in plasma, and compartmental models were developed accordingly. Plasma zinc exchanged more rapidly with zinc in liver and kidneys than it did with zinc in textes, skeletal muscle, or bone. Total body zinc content (2.6 mg/100 g live body weight) measured chemically was about 9 times higher than estimates of exchangeable zinc in the body. Whole-body retention of 65Zn was higher and endogenous fecal zinc excretion was lower in rats fed phytate than in those fed the basal diet; these responses to phytate may reflect a homeostatic adjustment to decreased absorption of zinc. Respective values for apparent absorption and true absorption of zinc were 13 and 32% of zinc intake in rats fed phytate, and 19 and 46% of zinc intake in rats fed the basal diet. When whole grains or mature seeds constitute a major portion of the diet, the phytate:zinc molar ratio may approach that (60:1) used in our study. Whether or not phytic acid occurring naturally in foods affects zinc metabolism to the same extent as sodium phytate can not be determined from our study.zinc absorption zinc retention endogenous zinc excretion zinc metabolism zinc kinetics phytate

Total True Efficiency of Zinc Utilization: Determination and Homeostatic Dependence upon the Zinc Supply Status in Young Rats

Total true efficiency of zinc utilization and its component factors, true absorption and metabolic efficiency, were studied in relation to dietary zinc supply in a 15-day experiment with 36 weanling rats in six groups. After day 3, the initial supply of 18.2 ppm zinc in the diet for all groups was changed to 5.6, 10.6, 18.2, 39, 70 and 141 ppm in groups 1 to 6, respectively. During the 6-day balance period after day 9, zinc intake was proportional to dietary zinc concentration. Mean daily rates of weight gain and apparent zinc retention increased from a near zero level in group 1 to a high plateau from group 4 to 6. True absorption rate steadily rose and reached about twice that of apparent absorption in group 6. This difference in rates was due to endogenous zinc excretion. Percent total utilization and percent true absorption steadily declined from a mean of about 100 in groups 1 and 2 to nearly 15 and 30, respectively, in group 6. Metabolic efficiency, reflecting true retention of absorbed zinc, similarly declined as percent true absorption did. The major conclusion was that not only the absorptive but also the metabolic efficiency greatly contributed to zinc homeostasis and total true efficiency of zinc utilization.

Zinc Absorption in the Rat Determined by Radioisotope Dilution

Zinc absorption in rats was examined by use of an isotope dilution technique. Young rats and mature rats fed varying levels of dietary zinc were injected intramuscularly with 65Zn. Nine days later, a zinc balance study was begun and continued for 5 days. The rats were then decapitated and the intestines and kidneys were removed and analyzed for zinc and 65Zn content. The feces were analyzed for zinc and 65Zn content and the specific activities of the intestines and kidneys were used to compute the contribution of endogenous zinc to total daily zinc excretion and thus calculate the true daily absorption of zinc. The zinc concentration of the intestines and kidneys did not differ significantly among groups but the specific radioactivity in these organs decreased as dietary zinc intake increased. Endogenous zinc excretion was greatest in mature rats and young rats fed the highest level of dietary zinc. Mature rats actually absorbed as much or more zinc than young rats fed the same dietary level of zinc. The results demonstrate that zinc homeostasis in rats is maintained by zinc secretion from the intestine rather than by regulation of zinc absorption.

UNUSUAL EFFECT OF SOME α‐MERCAPTOACRYLIC ACIDS ON METABOLISM OF ZINC IN THE RAT

1. Gavage of rats with beta-aryl derivatives of alpha-mercaptoacrylic acid resulted in pronounced and sustained elevation of serum zinc concentration. Greater than ten-fold increases above normal zinc levels were attained 2-8 h after doses of 50 mg/kg of the phenyl and furan derivatives. 2. These compounds were rapidly absorbed from the rat gastrointestinal tract and could be detected in serum for several days after a single dose. The return of serum zinc concentration to the normal level paralleled clearance of the mercaptoacrylic acid from plasma. 3. Close to 100% of the zinc and of the alpha-mercapto-beta-(2-furan)acrylic acid (MFA) in serum 4 h after administration of the compound were bound to serum macromolecules. 4. MFA decreased excretion of endogenous zinc; it altered neither the gastrointestinal absorption of zinc nor serum concentrations of copper, albumin and total protein. 5. These compounds appear to mobilize zinc from tissue stores and retard zinc clearance from plasma.

Zinc metabolism and homeostasis in rats fed a wide range of high dietary zinc levels.

Zinc metabolism and homeostasis were studied in young growing rats fed a 38 ppm zinc diet with added zinc levels ranging from 0 to 8400 ppm for 21 days. High dietary zinc did not cause toxicity symptoms. Stable zinc in feces increased linearly with dietary zinc intake but fecal 65Zn, from a single oral dose, did not increase above the 1200 ppm dietary level. Stable zinc in liver, kidney, and tibia increased two to three times with 2400 ppm added zinc, but was not further elevated until 8400 ppm was fed. Stable zinc in muscle and heart was not affected appreciably by dietary zinc level. In all tissues, 65Zn retention was drastically reduced with 1200 ppm added dietary zinc. Additional dietary zinc reduced 65Zn in muscle and heart but had little effect on liver and kidney 65Zn. The data indicate that rats have fairly effective homeostatic control mechanisms for tissue zinc below about 7200 ppm dietary zinc. Whereas, with dietary zinc up to about 1200 ppm, decreasing absorption is the main route of homeostatic control, above this level, more rapid zinc turnover rates and increasing endogenous zinc excretion appear to have major importance.

Radioisotope dilution technique for determination of zinc absorption in vivo.

A radioisotope dilution technique was adapted for determination of the absorbability of dietary zinc. In 16 growing rats given a casein diet with 12.8 mg Zn/kg dry matter, a mean apparent Zn digestibility of 72.4% was observed in a 6-day balance period 9 days after an intramuscular injection of 65Zn-ZnCl2. There was no significant difference in the specific radioactivity of zinc in blood plasma on day 15 and in urine collected from day 9 to day 15 used to assess the fecal excretion of endogenous zinc. Consequently, there was good agreement between the corresponding mean zinc absorbability (94.8 vs. 95.3%) calculated from these data.

Role of Pancreas in Endogenous Zinc Excretion in the Bovine

Role of Pancreas in Endogenous Zinc Excretion in the Bovine

Endogenous Zinc Excretion and 65Zn Metabolism in Holstein Calves Fed Intermediate to High but Nontoxic Zinc Levels in Practical Diets

Zinc and 65Zn metabolism, from a single intravenous dose (given 7 days after diets were initiated) were studied in Holstein bull calves fed a practical diet containing 38 ppm zinc or the same diet with 200 or 600 ppm supplemental zinc (zinc oxide). The supplemental zinc increased endogenous fecal 65Zn excretion by 30% with 200 ppm added zinc having as much influence as 600 ppm. The supplemental zinc had a very variable effect on 65Zn distribution in different tissues 14 days after dosing. With some tissues including testicle, rumen wall and abomasum (fundic) each increase in dietary zinc reduced 65Zn content. In muscle, dietary zinc level had no effect on 65Zn concentration. Adding 200 ppm zinc to the diet increased 65Zn and stable zinc in pancreas, liver and kidney; however, a further increase to 638 ppm caused very large increases in these tissues indicating a breakdown in homeostatic control for both injected and absorbed zinc. With the 638 ppm diet smaller increases in 65Zn occurred in bone and small intestine. Serum 65Zn increased with the high zinc diet. Except for muscle, where there was no change, specific activity in every tissue studied decreased with each increase in dietary zinc.

Zinc Metabolism in Alcoholic Liver Disease

Zinc metabolism was studied in 10 alcoholic cirrhotic patients following intravenous injection of zinc 65. Kinetic analysis was performed assuming a two-compartment open system. Values for miscible zinc pool, renal zinc clearance, total zinc turnover, endogenous zinc excretion, and "internal loss" were determined. Comparison with available kinetic data in normal subjects suggests a diminution in pool size and a slower turnover of zinc in these cirrhotic patients. Thus the kinetic data are compatible with the concept of zinc deficiency as a consistent abnormality in this type of cirrhosis. All patients studied had severe hepatic dysfunction but there was little correlation of clinical status with the measurements of zinc metabolism except for the serum zinc level that was within normal limits in the least ill patients. An increased renal clearance of zinc was found in all patients regardless of serum level. A consistent lag period between isotopic equilibrium in urine and plasma suggests that the urinary zinc is more a product of renal cellular zinc turnover than of glomerular filtration.