Influence of zinc depletion and zinc status on serum growth hormone levels in rats

In a preceding trial, the growth hormone concentrations in the serum of zinc-deficient rats were greatly reduced compared to thead libitum- fed control animals. The same reduction, however, was also noted in the case of the pair-fed control animals with strongly diminished feed intake. Therefore, it was not possible to distinguish between the effects of zinc deficiencyper se and the effects resulting from restricted feed intake. A new study with 136 young male Sprague-Dawley rats showed again that zinc deficiency as well as strongly restricted feed intake reduced the growth hormone content in the serum. But in a marginal zinc deficiency status, when feed intake was only slightly or not reduced, there were lowered serum growth hormone levels in comparison to pair-fed control rats. A 1-wk zinc repletion did not increase the serum growth hormone content of the rats to a normal level, although the serum zinc concentration was normalized.     

Iron,copper, and zinc status in rats fed supplemental nickel

Literature data concerning the effect of increasing dietary Ni concentrations on Fe, Cu, and Zn status in rats are sparse and, in part, controversial. Therefore, the effects of the addition of either 0, 3, 50, or 100 mg Ni/kg diet on Fe, Cu, and Zn status of rats were investigated in two separate experiments. Purified diets were used that were composed according to the established nutrient requirements of rats. Ni in kidney was increased with increasing Ni intakes. Dietary Ni did not significantly influence Fe concentrations in plasma, liver, kidney, femur, and spleen. Likewise, the addition of Ni to the diet did not alter Cu status. Zn concentrations in femur were significantly decreased after feeding the diets with 100 mg Ni/kg. However, Zn in plasma, liver, kidney, and spleen was not affected. It is concluded that variations in dietary Ni concentrations have no major impact on Fe, Cu, and Zn status in rats.     

Idiorrhythmic zinc dose-rate induction of intestinal metallothionein in rats depends upon their nutritional zinc status(dagger)

The idiorrhythmic dose-rate feeding experimental model was used to study the induction of intestinal metallothionein (iMT) by zinc (Zn) in the gastrointestinal (GIT) mucosa of young growing male rats relative to their nutritional Zn status. The idiorrhythmic approach requires that the average dietary Zn concentration, referred to as modulo (M), is kept constant across different groups over the whole experimental epoch (E). This is done by adjusting the Zn concentration of the supplemented diet to compensate for the reduction in the number of days on which this diet is fed, the latter being spread evenly over the whole experiment. Idiorrhythms (I) involve offering the diet with n times the overall Zn concentration (M) only every nth day with a Zn-deficient diet offered on other days. We studied three modulos (low-Zn, M3; adequate-Zn, M12; and high-Zn, M48), each M having 8 analogous idiorrhythms (I = Mx/1 to 8Mx/8); every I was fed over a 48-d idiorrhythmic E. Over the wide range of peak doses of dietary Zn (3-384 mg Zn/kg diet), the higher the modulo, the greater the capacity for iMT to be induced (M3 < M12 < M48; P < 0.05). Also, the ability of Zn to induce iMT increased proportionally with the progression of the idiorrhythms from I = Mx/1 to 8Mx/8 (P < 0.001). When rats were fed M3, less Zn was required to induce iMT than when they were fed M12 or M48. Thus, within the M and E limits of this study, the better the nutritional Zn status of the animal, the more Zn is required to induce iMT and vice versa. The fact that iMT was increased means that the amount of available Zn was not proportional with the actual steady state of its metabolism. This indicates that for any Zn supplementation program to be effective, it should progress gradually from a lower to a higher Zn dose relative to the given nutritional Zn status.     

Kinetics of zinc status and zinc deficiency in Berardinelli-Seip syndrome

Berardinelli-Seip syndrome (BSS) is a very rare disorder characterized by near-complete absence of adipose tissue from birth or early infancy, hypoleptinemia, hypertriglyceridemia, insulin resistance, diabetes mellitus, and other clinical signals. It is caused by mutations in AGPAT2 or Gng3lg. We evaluated 10 BSS patients and 10 healthy subjects. A single dose of 382.43 μmol zinc was administered intravenously before and after 3 months of oral zinc supplementation. Blood samples were collected from the contralateral arm at 0, 30, 60, 90, and 120 min after zinc injection. Plasma and serum were obtained to measure hematological and biochemical parameters. Urine was collected to measure creatinine, protein, and zinc. Basal serum zinc levels were similar in controls and BSS patients. However, serum zinc profiles were significant reduced in BSS patients in comparison with controls. The change in total-body zinc clearance was more significant in BSS patients, indicating that these patients had suboptimum zinc deficiency.     

The combined effect of high iron and zinc intake on copper status in rats

The interactions between copper, zinc, and iron intake in rats were investigated with regard to copper status. Weanling male rats were fed purified diets containing two levels of each of the three elements in a 2³ factorial design. The added amounts of copper, zinc, and iron in the diets were 5, 12, and 35 mg/kg feed or were 10 times as high. After feeding on the experimental diets for 4 wk, the rats were killed and copper concentrations in plasma and organs measured. Plasma copper concentration was lowered by high zinc and iron intakes but this was seen only in the rats fed the normal-copper instead of the high-copper diets. In essence, the effects of zinc and iron were additive. Neither in rats fed the normal-copper diets nor in those fed the high-copper diets did extra iron or zinc intake alter copper concentrations in liver, spleen, kidney, and tibia.     

Dietary zinc restriction in rats alters antioxidant status and increases plasma F2 isoprostanes

Approximately 12% of Americans do not consume the estimated average requirement for zinc and could be at risk for zinc deficiency. Since zinc has proposed antioxidant function, inadequate zinc consumption may lead to an enhanced susceptibility to oxidative stress through several mechanisms, including altered antioxidant defenses. In this study, we hypothesized that dietary zinc restriction would result in lower antioxidant status and increased oxidative damage. We fed weanling Sprague-Dawley rats (n=12 per group) a zinc-adequate (50 mg/kg of zinc) diet, a zinc-deficient (<0.05 mg/kg of zinc) diet or a pair-fed diet for 3 weeks and then assessed their antioxidant status and oxidative stress parameters. Rats were zinc deficient as indicated by a significant (P<.05) reduction in body weight (49%) and 19% lower (P<.05) hepatic zinc (20.6+/-2.1 mg/kg) as compared with zinc-adequate rats (24.6+/-2.2 mg/kg). Zinc deficiency resulted in elevated (P<.05) plasma F(2) isoprostanes. Zinc deficiency-mediated oxidative stress was accompanied by a 20% decrease (P<.05) in the ferritin-reducing ability of plasma assay and a 50% reduction in plasma uric acid (P<.05). No significant change in plasma ascorbic acid or in plasma alpha-tocopherol and gamma-tocopherol was observed. However, hepatic alpha-tocopherol and gamma-tocopherol concentrations were decreased by 38% and 27% (P<.05), respectively, as compared with those in zinc-adequate rats. Hepatic alpha-tocopherol transfer protein levels were unaltered (P>.05) by zinc deficiency, but cytochrome P450 (CYP) 4F2 protein levels were elevated (P<.05) as compared with those in zinc-adequate rats. Collectively, zinc deficiency increased oxidative stress, which may be partially explained by increased CYP activity and reductions in hepatic alpha-tocopherol and gamma-tocopherol and in plasma uric acid.     

Assessment of copper and zinc status in hair and urine of young women descendants of NIDDM parents

The concentration of copper (Cu) and zinc (Zn) in hair and urine were studied in young nonpregnant healthy women whose both parents were diagnosed for noninsulin-dependent diabetes mellitus (NIDDM descendants) and were compared with those of young healthy nonpregnant females with no family history of NIDDM or hypertension (non-NIDDM descendants) and NIDDM patients. The concentration of Zn in hair in NIDDM descendants was significantly higher than that of non-NIDDM descendants (p < 0.001) and insignificantly higher than that of NIDDM patients. The hair Cu concentrations in NIDDM descendant and patients were significantly lower than that of non-NIDDM descendants (p < 0.001). Hyperzincuria was detected in some NIDDM patients and hypocuperuria in all NIDDM descendants and patients. The data suggest that the young healthy NIDDM descendants possess high-Zn and low-Cu reserves in their bodies, and the observed perturbation appears to be associated with Cu-Zn antagonism.     

Nuclear zinc in liver of cadmium and zinc treated rats

X-ray microanalysis was performed to detect quantitatively, the variation of the nuclear zinc in the liver cells of rats. The nuclear zinc concentration showed statistical decrease and increase in response to cadmium and zinc treatments, respectively. The results suggest that the liver responds differently to cadmium and zinc treatments. The difference in response to either treatment may reflect different mechanisms of zinc transport and metabolism in the liver. The difference in binding affinity of metallothionein (MT) may suggest the involvement of Mt in the metabolism and transport of zinc, an effect, which may be modified by treatment.     

Cadmium accumulation, zinc status, and mineral bioavailability of growing rats fed diets high in zinc with increasing amounts of phytic acid

Five groups of individually housed albino rats (n=7, initial average weight=48 g) were fed diets based on egg albumen and cornstarch (basal diet 8.2 g Ca, 6.0 g P, 0.7 g Mg, 225 mg Zn, 150 mg Fe, 60 mg Mn, 8 mg Cu, and 5 mg Cd) over a 4-wk period. Group I (control) was fed the basal diet free of phytic acid (PA). In groups II, III, IV, and V, cornstarch was replaced by 3.5, 7.0, 10.5, and 14.0 g sodium phytate/kg diet, respectively. Daily gain, feed efficiency, Zn status (Zn in plasma, femur, testes, liver and kidneys, activity of the plasma alkaline phosphatase) and apparent absorption of Zn, Fe, Cu, and Mn remained unchanged by the different dietary treatments. PA decreased apparent Mg absorption significantly and apparent absorption of Ca in tendency. Increasing the amount of phytate caused a corresponding enhancement of amount of the digestible P. Cd accumulation in the liver was not significantly altered, and kidney Cd accumulation slightly increased owing to PA. In conclusion, it was shown that under conditions of high dietary Zn, PA had only little effect on the carryover of Cd in growing rats.     

Iron and zinc status in rats with diet-induced marginal deficiency of vitamin A and/or copper

The hypothesis was tested that there are interactions of marginal copper and vitamin A deficiency regarding iron and zinc status. Copper restriction (1 vs 5 mg Cu/kg diet) significantly lowered copper concentrations in plasma and tissues of rats and reduced blood hemoglobin, hematocrit, and iron concentrations in tibia and femur, but raised iron concentrations in liver. Vitamin A restriction (0 vs 4000 IU vitamin A/kg diet) reduced plasma retinol concentrations and induced a fall of blood hemoglobin and hematocrit. Neither copper nor vitamin A restriction for up to 42 d affected feed intake and body wt gain. There were no interrelated effects of vitamin A and copper deficiency on iron status. Copper deficiency slightly depressed liver, spleen, and kidney zinc concentrations. Vitamin A deficiency lowered zinc concentrations in heart, but only when the diets were deficient in copper.     

Dietary zinc status reversibly alters both the feeding behaviors of the rats and gene expression patterns in diencephalon

Nutritional status influences feeding behaviors, food preferences, and taste sensations. For example, zinc-deficient rats have been reported to show reduced and cyclic food intake patterns with increased preferences for NaCl. Although some impairments of the central nervous and endocrine systems have been speculated to be involved in these phenomena, the effects of short-term zinc deficiency on the brain have not been well examined to date. In this study, we performed a comprehensive analysis of the gene expression patterns in the rat diencephalon, which is a portion of the brain that includes the hypothalamus and thalamus, after short-term zinc deficiency and also during zinc recovery. The rats showed reduced and cyclic food intake patterns with increased salt preferences after a 10-day dietary zinc deficiency. A comparative analysis of their diencephalons using cDNA microarrays revealed that approximately 1% of the genes expressed in the diencephalons showed significantly altered expression levels. On the other hand, a 6-day zinc supplementation following the deprivation allowed for the recovery to initial food intake behaviors and salt preferences. The expression levels of most of the genes that had been altered by exposure to zinc deficient conditions were also recovered. These results show that feeding behaviors, taste preferences and gene expression patterns in the diencephalon respond quickly to changing zinc levels.     

Influence of zinc on the status of hepatic trace elements and biokinetics of 65Zn in ethanol treated rats

Whole body counting studies of 65Zn indicated that the Tb1 (the faster component) was significantly decreased while the slower component (Tb2) was increased significantly following ethanol treatment. Interestingly, following zinc treatment to ethanol treated rats, slower component (Tb2) of 65Zn came back to within normal limits while the faster component (Tb1) got significantly elevated in comparison to ethanol treatment. Percent uptake values of 65Zn were found to be increased in liver, intestine, muscle, brain and kidney, and decreased in bone under alcoholic conditions. Interestingly, the uptake values of 65Zn in all the organs except muscle were reverted back to within normal limits upon zinc supplementation to these ethanol intoxicated animals. A significant decrease in zinc contents was noticed in ethanol treated rats, which, however, were raised to normal levels upon zinc supplementation: Copper levels, on the other hand, were significantly enhanced in both ethanol fed and combined ethanol + zinc treated rats. Calcium levels were significantly decreased in both ethanol and zinc treated rats, which however were further reduced upon zinc supplementation to ethanol fed rats. However, no significant change was observed in the concentrations of sodium and potassium in any of the treatment groups. In conclusion, zinc appears to play a protective role by normalizing the turnover of 65Zn in whole body as well as in its uptake in different organs under alcoholic conditions.     

Assessment of reproductive status in male echidnas

This study reports the development and application of techniques to assess the reproductive status of male echidnas. The pattern of testosterone secretion over a 24-h period in five echidnas was documented. Testosterone secretion after injection i.m. of either 1000 IU hCG (n=4) or 4 microg GnRH agonist (n=6) was determined to establish whether this could be used as a practical index of the prevailing steroidogenic capacity of the testes. hCG (1000 IU) was also used to assess seasonal changes in testosterone secretion in six echidnas over a 13-month period. Seasonal changes in testicular volume were examined by transabdominal ultrasonography. Electroejaculation was attempted to monitor seasonal changes in sperm production, which was also determined by spermatorrhea. There was no apparent diurnal pattern of testosterone secretion in echidnas and circulating concentrations of testosterone remained relatively low (maximum 1.2 ng/mL) and stable over 24h. Injection of hCG resulted in an increase (P<0.01; n=4) in testosterone concentration with a peak (2.9+/-0.3 ng/mL) approximately 4h after injection. GnRH also induced an increase (P<0.01; n=6) in circulating testosterone that was apparent after 1h (2.6+/-0.3 ng/mL) and concentrations remained elevated (3.4+/-0.3 ng/mL) for up to 8h after injection. Seasonal changes in testosterone secretion determined after injection of hCG, increased (P=0.03; n=6) from late-autumn, peaked in late-winter, and decreased by early-spring. Testicular volume followed a similar seasonal pattern (P<0.01; n=6) with an increase from late-autumn, peak in winter and a decline in mid-spring. There was no seasonal change in live weight. Electroejaculation was attempted throughout two breeding seasons but no semen was obtained. Spermatorrhoea in the echidna was described for the first time and was subsequently used to assess seasonal sperm production. Spermatozoa were found in the urine from June to September. This study has demonstrated that exogenous hormones can be used to obtain an index of the prevailing steroidogenic capacity of the testes in echidnas, which is not apparent with repetitive non-stimulated samples over 24 h. The assessment of testosterone secretion after injection of trophic hormones provides a valuable and practical procedure for the assessment of reproductive status. Testicular ultrasonography and spermatorrhea are useful in assessing reproductive status and in this study were successfully used to determine seasonal reproduction in captive echidnas.     

Interaction between zinc and iron in rats

The importance of interactive effects, of minerals in general, on nutrient requirements is becoming increasingly recognized. The interaction between iron and zinc has not been as widely investigated. The metabolic interrelationships between dietary iron and zinc have been known for years, but some subtle relationships may have gone unrecognized. Because nutrient interactions are not necessarily linear in nature, it may be inadequate to apply linear statistical models to study the interaction between zinc and iron. In this study, we used traditional as well as a nonlinear approach in analyzing experimental results from groups of rats fed a wide range of dietary zinc and iron. Male weanling Sprague-Dawley rats were used in a 5 × 4 factorially arranged experiment. Dietary variables were iron (as ferric citrate) at 4, 12, 24, 48, or 96 μg Fe/g diet and zinc (as zinc carbonate) at 5, 10, 20, or 40 μg Zn/g diet. After 7 wk, hematological parameters were measured and plasma ceruloplasmin and cholesterol were determined. In addition to interactive effects as shown by analysis of variance, the application of log-linear analysis to the experimental data revealed a far broader range of interactions between dietary iron and zinc. As a result of our experiment and its quantitative analysis, we conclude that the interaction between iron and zinc is nutritionally important and that dietary iron affected the response of many blood parameters to dietary zinc. The complete dataset can be found at http://www.gfhnrc.ars.usda.gov/fezn. U.S. Department of Agriculture, Agricultural Research Service, Northern Plains Area is an equal opportunity/affirmative action employer and all agency services are available without discrimination.     

Lead increases urinary zinc excretion in rats

The major purpose of this study was to determine whether acute or chronic Pb exposure would increase urinary excretion of zinc in the rat. Four groups of unanesthetized rats were given 0, 0.03, 0.3, or 3 mg Pb (as acetate) kg intravenously, and urinary excretion of zinc, sodium, and potassium was monitored for 6 h. Only at the highest dose was urinary Zn excretion significantly elevated; there were no significant changes in sodium and potassium excretion at any dose. Two other groups of rats were studied for 9 weeks in metabolism cages before and during administration of either 500 ppm Pb (as acetate) or equimolar Na acetate in the drinking water. Two days after Pb treatment and continuing through day 35, Zn excretion was elevated in the Pb-exposed animals; beyond this day, zinc excretion became similar in the two groups. The difference in Zn excretion was not the result of lower water intake by the Pb-treated animals. At sacrifice (70 days after starting Pb exposure), Pb-exposed animals had lower Zn content of the plasma and testis, but there was no difference in kidney Zn. Plasma renin activity was significantly higher in Pb-exposed animals. We conclude that chronic Pb exposure in rats can result in some degree of decreased tissue zinc, which is, at least in part, secondary to increased urinary losses of zinc.     

Gustatory preferences in zinc deficient adult rats

Fluid consumption and preference behavior were evaluated asa function of dietary zinc content during adulthood. Dietarytreatment of sixteen adult male rats was initiated 30 days priorto preference testing: eight rats were fed ad libitum a zinc-deficientdiet and eight rats were match-fed a zincreplete diet. Preferencetesting was performed using a 96-hour, two bottle free-choicetechnique. Rats were exposed to each of the following tastant-containingsolutions for successive 4-day periods: 1.5, 3.0, and 4.5x10^–1M sodium chloride; 1.0x10^–2 M sucrose; 2.5x10^–3M hydrochloric acid, and 1.28x10^–6 M quinine sulfate. The two groups had essentially equivalent weights prior to thedietary manipulation. The zinc-deficient rats weighed significantlyless than replete rats throughout preference testing, but didnot appear as physically debilitated as do weanling rats feda zinc-deficient diet for equivalent durations. The deficientrats demonstrated increased preferences for most of the tastantsolutions, accompanied by increased total volume intakes. Thesealterations were attributable to increases in tastant volumeintake by the deficient rats while water intake remained normal.Results were interpreted as supporting the hypothesis that zincdeficiency decreases gustatory sensitivity; however, the etiologyof this effect remains unclear.     

Consecutive zinc balance trials in growing rats

Rats were fed a purified egg white-based diet containing 5 ppm Cu and 2, 14, or 57 ppm Zn. Zinc and copper balances were determined for eight consecutive weekly trial periods. The zinc-deficient group almost ceased to gain weight and was in slightly negative zinc balance. Groups of rats fed 14 and 57 ppm Zn gained weight at equal rates. These groups were in strongly positive zinc balance for four weeks; thereafter, they fed 57 ppm Zn retained about two times as much zinc as did the group fed the diet containing 14 ppm Zn. All groups were in null or slightly negative copper balance throughout the trial. These results suggest that zinc accumulation may be homeostatically controlled to a level in excess of that needed for maximum growth.     

Excess calcium increases bone zinc concentration without affecting zinc absorption in rats

We examined zinc (Zn) metabolism in rats given diets containing excess calcium (Ca). Rats were given phytate-free diet containing 5 g Ca/kg (control), 12.5 g Ca/kg, or 25 g Ca/kg for 4 wk in Experiment 1. The dietary treatment did not affect Zn concentration in the plasma, testis, kidney, spleen and liver; however, Zn concentration in the femur and its cortex was significantly higher in rats given diet containing 25 g Ca/kg than in other rats. Rats were given phytate-free diet containing 5 g Ca /kg or 25 g Ca /kg for 4 wk in Experiment 2. After 12-h food deprivation, rats were given a diet extrinsically labeled by 67Zn with dysprosium as a fecal marker for 4 h. Feces were collected from 1 d before administration of the labeled diet to 5 d after administration. Excess Ca did not affect the true absorption of Zn and its endogenous excretion but increased femoral Zn. These results suggest that excess Ca improves Zn bioavailability without affecting Zn absorption when diets do not contain phytate.