Zinc metabolism in genetically obese (ob/ob) mice

Recent reports indicate that the concentrations and total amounts of several essential trace metals in various tissues of genetically obese rodents differ markedly from those in lean controls. In the present studies the absorption, retention and tissue distribution of zinc and constitutive levels of zinc-metallothionein (Zn-MT) in selected tissues were compared in obese (ob/ob) and lean (+/?) C57BL/6J mice. When 5-, 10- and 22-wk-old mice were administered 1.2 mumol 65Zn by stomach tube the apparent absorption of 65Zn by obese mice was 1.5, 2.2 and 3.9 times higher, respectively, than that in age-matched lean mice. Retention of orally administered 65Zn after 96 h was also substantially higher in obese mice than in lean mice. To assess the possible influences of hyperphagia and intestinal hypertrophy on the enhanced apparent absorption of 65Zn by obese mice food intake by an additional group of obese mice was restricted to that of age-matched lean controls. When actual absorption of zinc was determined according to the method of Heth and Hoekstra, groups of ad libitum--fed obese, pair-fed obese and lean mice absorbed 38, 32 and 18% of administered 65Zn, respectively. In contrast, the rate of 65Zn excretion 2-6 d after oral or subcutaneous administration of the metal was similar for obese and lean mice. Unrestricted and pair-fed obese mice had significantly lower percentages of carcass 65Zn present in skin, muscle plus bone, spleen and testes and higher percentages present in liver, small intestine and adipose tissue than lean mice.(ABSTRACT TRUNCATED AT 250 WORDS)     

Zn-depleted mice absorb more of an intragastric Zn solution by a metallothionein-enhanced process than do Zn-replete mice

The influence of metallothionein (MT)(2) on Zn absorption was investigated in MT-null (MT-/-) and normal (MT+/+) mice fed Zn-depleted (ZnD) diets for 7 d and compared with those fed Zn-replete (ZnR) diets in a previous study. Mice were starved for 20 h, then administered an oral gavage of aqueous (65)ZnSO(4) solution at doses of 154, 770 or 1540 nmol of Zn, and the amount transferred into nongut tissues was determined 4 h later. (65)Zn transfer did not differ between genotypes in ZnR mice. However ZnD MT+/+ mice had a 30-40% greater transfer from the 154 and 770 Zn doses compared to ZnR MT+/+ mice. This was not observed in MT-/- mice. In MT+/+ mice, Zn depletion enhanced the induction of MT by Zn in the intestine and pancreas. (65)Zn uptakes in the liver and pancreas were greater in MT+/+ than MT-/- mice, and this was greater (50%) at the 154 and 770 doses in mice fed ZnD diets. Plasma Zn concentrations were raised to a similar extent in ZnR and ZnD MT-/- mice. ZnR MT+/+ mice had significantly lower plasma Zn levels than MT-/-mice; this difference was less marked in the ZnD mice. We conclude that a MT-facilitated enhancement in Zn absorption occurs in response to dietary Zn deficiency.     

Relationship of cytotoxic activity of natural killer cells to growth rates and serum zinc levels of female RIII mice fed zinc

This study examined a) the dietary zinc (Zn) requirement of RIII female weanling mice and b) the cytotoxicity of murine natural killer (NK) cells obtained from spleens of these mice fed varying levels of Zn. Zn was fed in a biotin-enriched egg albumen diet in amounts ranging from 0.9 to 40.4 micrograms/g diet. During a 28-day growth assay, maximum carcass growth was obtained with a diet containing 5.4 micrograms Zn/g diet. Maximal serum levels of Zn, however, were observed in mice fed diets containing 3.4 micrograms Zn/g diet. The cytotoxic activity of NK cells obtained from spleens of selected treatment groups was maximal at 40.4 micrograms Zn/g diet and was significantly higher (p less than or equal to 0.05) than that observed in spleens from mice fed diets that maximized carcass growth rates and serum Zn concentrations. It is concluded that female RIII mice have a dietary Zn requirement for growth similar to that observed for other murine strains but considerably lower than that reported for the rat. Our findings also suggest that RIII NK cells are particularly sensitive to dietary Zn intake: the optimal functional activity of these cells may result from intake of Zn higher than that necessary to maximize carcass growth and serum Zn concentrations.     

Relationship of cytotoxic activity of natural killer cells to growth rates and serum zinc levels of female RIII mice fed zinc

This study examined a) the dietary zinc (Zn) requirement of RIII female weanling mice and b) the cytotoxicity of murine natural killer (NK) cells obtained from spleens of these mice fed varying levels of Zn. Zn was fed in a biotin‐enriched egg albumen diet in amounts ranging from 0.9 to 40.4 μg/g diet. During a 28‐day growth assay, maximum carcass growth was obtained with a diet containing 5.4 μg Zn/g diet. Maximal serum levels of Zn, however, were observed in mice fed diets containing 3.4 μg Zn/g diet. The cytotoxic activity of NK cells obtained from spleens of selected treatment groups was maximal at 40.4 μg Zn/g diet and was significantly higher (p ≤ 0.05) than that observed in spleens from mice fed diets that maximized carcass growth rates and serum Zn concentrations. It is concluded that female RIII mice have a dietary Zn requirement for growth similar to that observed for other murine strains but considerably lower than that reported for the rat. Our findings also suggest that RIII NK cells are particularly sensitive to dietary Zn intake: the optimal functional activity of these cells may result from intake of Zn higher than that necessary to maximize carcass growth and serum Zn concentrations.     

Effects of herring roe on plasma lipid, glucose, insulin and adiponectin levels, and hepatic lipid contents in mice

We previously reported that lipids extracted from salted herring roe product (Kazunoko), which contains large amounts of cholesterol, phosphatidylcholine and n-3 polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3), decreased plasma lipid and glucose concentrations in mice. The aim of this study was to evaluate the effects of Kazunoko containing large amounts of protein on lipid and glucose metabolism in mice. Male Crlj:CD-1 (ICR) mice were fed three experimental diets containing lyophilized Kazunoko for 12 wk. The experimental diets were as follows: without Kazunoko (control diet); 1% Kazunoko (1% Kazunoko diet); and 4% Kazunoko (4% Kazunoko diet). Plasma total cholesterol, phospholipid and glucose concentrations tended to be lower in the 1% and 4% Kazunoko diet groups than in the control diet group. There were significant differences in plasma glucose concentration between the control and 4% Kazunoko diet groups (p<0.05). Plasma adiponectin concentrations in mice fed the 4% Kazunoko diet were also significantly higher than in those fed the control diet (p<0.05), but there were no marked differences in plasma insulin concentration among the three dietary groups. Hepatic total cholesterol and phospholipid contents tended to be lower in the 4% Kazunoko diet group than in control diet group. Plasma and hepatic n-3/n-6 ratios in the 1% Kazunoko diet and 4% Kazunoko diet groups were significantly higher when compared with those of the control diet group (p<0.005 and p<0.0005, respectively). These results suggest that ingestion of Kazunoko influences lipid and glucose metabolism in mice fed the Kazunoko diets, as compared with animals fed the control diet.     

Total zinc absorption in young women, but not fractional zinc absorption, differs between vegetarian and meat-based diets with equal phytic acid content

Zn bioavailability is often lower in vegetarian diets mainly due to low Zn and high phytic acid contents. The objective of the present study was to determine the fractional and total absorption of Zn from a vegetarian diet in comparison with meat diets with equal concentrations of phytic acid. A randomized cross-over design, comprising three whole-day diet periods of 5 d each, with a vegetarian diet or diets containing Polish-produced meat or Danish-produced meat, was conducted. Twelve healthy female subjects completed the study. All diets had a high content of phytic acid (1250 micromol/d) and in the meat diets the main meals contained 60 g pork meat. All main meals were extrinsically labelled with the radioactive isotope 65Zn and absorption of Zn was measured in a whole-body counter. The mean Zn content of the whole-day diet was: Polish meat diet 9.9 (SE 0.14) mg, Danish meat diet 9.4 (SE 0.19) mg and vegetarian diet 7.5 (SE 0.18) mg. No difference was observed in the fractional absorption of Zn (Polish meat diet: 27 (SE 1.2) %, Danish meat diet: 27 (SE 1.9) % and vegetarian diet: 23 (SE 2.6) %). A significantly lower amount of total Zn was absorbed from the vegetarian diet (mean Zn absorption of Polish meat diet: 2.7 (SE 0.12) mg/d (P<0.001), Danish meat diet: 2.6 (SE 0.17) mg/d (P=0.006) and vegetarian diet: 1.8 (SE 0.20) mg/d). In conclusion, the vegetarian diet compared with the meat-based diets resulted in lower amounts of absorbed Zn due to a higher content of Zn in the meat diets, but no difference was observed in the fractional absorption of Zn.     

Effects of dietary protein, energy and tyrosine on central and peripheral norepinephrine turnover in mice

Norepinephrine (NE) turnover rate and tyrosine concentrations were assessed in several tissues of 5-wk-old female lean mice that were fed diets of 20% protein (1.2% tyrosine), 40% protein (2.4% tyrosine) or tyrosine-supplemented diets of 40% protein with 4 or 8% tyrosine or 20% protein with 4% tyrosine for 4 d. Mice fed the 40% protein diet had significantly lower NE turnover rates in interscapular brown adipose tissue, heart and kidney (66, 64 and 49%, respectively) and nonsignificantly lower (84%) turnover rate in brain than did mice fed the 20% protein diet, but plasma and tissue tyrosine concentrations did not differ. When energy intake of the 20% protein-fed mice was restricted to 92% of the 40% protein-fed mice, tyrosine concentration in plasma and tissues was lower by half, but NE turnover rate did not differ between the two groups. Supplementation of the 40 or 20% diets with tyrosine, resulting in twofold higher plasma and tissue tyrosine concentrations, had no effect on NE turnover rate in any organ examined. We conclude that both energy intake and dietary protein concentration affect sympathetic nervous system activity in young mice. Tyrosine does not mediate or alter these changes.     

Effect of varying dietary zinc intake of weanling mouse pups during recovery from early undernutrition on tissue mineral concentrations, relative organ weights, hematological variables and muscle composition

Because growth is an early sign of zinc (Zn) deficiency in young animals, it is often assumed that the occurrence of normal growth indicates adequate Zn status. In an earlier study we found that both marginal (10 micrograms Zn/g) and low (5 micrograms Zn/g) dietary Zn intake resulted in altered composition of gain in mouse pups that had been previously undernourished (L) from d 10 to 21 of suckling and rehabilitated from d 21 to 40 with high protein recovery diets. Therefore we examined several tissues, organs and biochemical measures to identify other variables that might be sensitive to either marginal or low dietary Zn intake in mice. After undernutrition in the suckling animal, liver Zn concentrations were lower; they normalized when the pups were subsequently fed recovery diets irrespective of dietary Zn intake (5-110 micrograms Zn/g). Bone Zn was 30% lower in pups fed low Zn, and 30% higher in pups given Zn-supplemented recovery diets (110 micrograms Zn/g) compared with controls (40 micrograms Zn/g). Thus bone Zn concentration was highly correlated with dietary Zn intake and lower liver Zn was highly correlated with undernutrition. Most organs of L pups recovered in proportion to body weight; the exceptions were brain, kidney and gastrocnemius muscle. At d 21 or 40, brain weight was most conserved and kidney weight was stunted during either protein or Zn deprivation. Gastrocnemius muscle weight in L pups was stunted to a much greater degree than other tissues, although proximate analysis showed muscle composition was similar among groups. These data support previous reports that adequate dietary Zn is essential for optimal recovery from early undernutrition.     

Effect of polychlorinated biphenyls on tissue distribution and intestinal absorption of alpha-tocopherol in rats

We conducted experiments to elucidate the mechanism by which alpha-tocopherol (alpha-toc) concentration in the liver remarkably increases in rats treated with polychlorinated biphenyls (PCB) when excess amounts of DL-alpha-tocopheryl-acetate (alpha-toc-ac) were given. First, diets containing 5 and 50 mg of alpha-toc-ac per 100 g were respectively added with 0.05% of PCB and given to rats for 10 days, and alpha-toc distributions in tissues were determined. Next, the disappearance of alpha-toc from a ligated intestine of vitamin E (E)-deficient rats was then studied. There were no significant differences between the control and the PCB groups in alpha-toc concentrations in the liver and other tissues except a few tissues when a lower level of alpha-toc-ac (5 mg) was given. Conversely, when a higher level of alpha-toc-ac (50 mg) was given, alpha-toc concentration in the liver of the PCB group significantly increased compared to that of the control group. This agrees with the result previously reported, showing a remarkable reproducibility. In addition, alpha-toc concentrations in tissues other than the liver were also significantly higher in the PCB group than in the control group. Transmigration of alpha-toc to the liver from other tissues was therefore excluded. The alpha-toc absorption test using the ligated intestine of E-deficient rats revealed that alpha-toc disappears from the intestine at a higher rate in the presence of PCB compared to the untreated control group. This may indicate that alpha-toc absorption by passive diffusion is accelerated in the coexistence of PCB.     

Influence of genetic obesity on tissue concentrations of zinc, copper, manganese and iron in mice

The concentrations (micrograms/gram dry wt) of four essential trace metals in various tissues from C57BL/6J lean (+/?) and obese (ob/ob) mice were determined. Lower concentrations of zinc were found in liver, femur, small intestine and muscle from obese mice than in those from lean mice at 22 wk of age. The concentrations of copper in liver, femur, small intestine, muscle and testes, iron in liver, femur, muscle and plasma, and manganese in liver, femur and small intestine from adult obese mice were also significantly below the concentrations present in tissues from age-matched lean mice. Hepatic concentrations of zinc, copper and manganese in obese mice were also lower than those in lean mice when the different amounts of neutral lipid in obese and lean liver were considered. In contrast with the trend towards lower concentrations of trace metals in tissues from adult obese mice, plasma zinc and copper levels and ceruloplasmin activity were higher in adult obese mice than in lean controls. The effect of genetic obesity on tissue trace metals concentrations was similar in male and female mice. Several tissues from young (5-6 wk of age) obese mice also had lower concentrations of the trace metals than age-matched lean mice, although the differences were not as great as in adults. These data demonstrate that chronic obesity in the genetically obese (ob/ob) mouse is associated with lower concentrations, but not necessarily lower total quantities, of several inorganic micronutrients in tissues. The possibility tht chronic obesity alters the nutritional requirements for these trace metals is discussed.     

Effect of reduced dietary zinc intake on carbohydrate and Zn metabolism in the genetically diabetic mouse (C57BL/KsJ db+/db+)

1. Male, 4-5-week-old, genetically diabetic mice (C57BL/KsJ db/db) and non-diabetic heterozygote littermates (C57BL/KsJ db/+) were fed on a diet containing 1 mg zinc/kg (low-Zn groups) or 54 mg Zn/kg (control groups) for 27 d. Food intakes and body-weight gain were recorded regularly. On day 28, after an overnight fast, animals were killed and blood glucose and insulin concentrations, liver glycogen, and femur and pancreatic Zn concentrations were determined. 2. The consumption of the low-Zn diet had only a minimal effect on the Zn status of the mice as indicated by growth rate, food intake and femur and pancreatic Zn concentrations. In fact, diabetic mice fed on the low-Zn diet had a higher total food intake than those fed on the control diet. The low-Zn diabetic mice had higher fasting blood glucose and liver glycogen levels than their control counterparts. Fasting blood insulin concentration was unaffected by dietary regimen. 3. A second experiment was performed in which the rate of loss of 65Zn, injected subcutaneously, was measured by whole-body counting in the two mouse genotypes over a 28 d period, from 4 to 5 weeks of age. The influence of feeding low-Zn or control diets was also examined. At the end of the study femur and pancreatic Zn and non-fasting blood glucose levels were determined. 4. All mice fed on the low-Zn diet showed a marked reduction in whole-body 65Zn loss compared with those animals fed on the control diet.(ABSTRACT TRUNCATED AT 250 WORDS)     

Growth and zinc homeostasis in the severely Zn-deficient rat

Male weanling rats were fed on diets either adequate (55 mg/kg), or severely deficient (0.4 mg/kg) in zinc, either ad lib. or in restricted amounts in four experiments. Measurements were made of growth rates and Zn contents of muscle and several individual tissues. Zn-deficient rats exhibited the expected symptoms of deficiency including growth retardation, cyclic changes in food intake and body-weight. Zn deficiency specifically reduced whole body and muscle growth rates as indicated by the fact that (a) growth rates were lower in ad lib.-fed Zn-deficient rats compared with rats pair-fed on the control diet in two experiments, (b) Zn supplementation increased body-weights of Zn-deficient rats given a restricted amount of diet at a level at which they maintained weight if unsupplemented, (c) Zn supplementation maintained body-weights of Zn-deficient rats fed a restricted amount of diet at a level at which they lost weight if unsupplemented (d) since the ratio, muscle mass: body-weight was lower in the Zn-deficient rats than in the pair-fed control groups, the reduction in muscle mass was greater than the reduction in body-weight. Zn concentrations were maintained in muscle, spleen and thymus, reduced in comparison to some but not all control groups in liver, kidney, testis and intestine, and markedly reduced in plasma and bone. In plasma, Zn concentrations varied inversely with the rate of change of body-weight during the cyclic changes in body-weight. Calculation of the total Zn in the tissues examined showed a marked increase in muscle Zn with a similar loss from bone, indicating that Zn can be redistributed from bone to allow the growth of other tissues. The magnitude of the increase in muscle Zn in the severely Zn-deficient rat, together with the magnitude of the total losses of muscle tissue during the catabolic phases of the cycling, indicate that in the Zn-deficient rat Zn may be highly conserved in catabolic states.     

Effect of tumor weight and tube feeding on TNF-alpha and IL-1beta mRNA expression in the brain of mice.

BACKGROUND: Previous studies have shown that cytokine mRNA expression is elevated in the brains of anorectic, tumor-bearing rats. The objectives of the current study were as follows: (1) to determine whether a small tumor would result in up-regulation of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta mRNA expression in the brain and other tissues of tumor-bearing mice; and (2) to determine whether hyperalimentation by tube feeding would prevent up-regulation of cytokine mRNA expression in the brain and other tissues of tumor-bearing mice. METHODS: Male C57BL/6 mice were divided into 4 groups: (1) control mice fed ad libitum (Control); (2) tumor-bearing mice fed ad libitum (TB); (3) control mice receiving tube feeding (CTF); and (4) tumor-bearing mice receiving tube feeding (TBTF). RESULTS: TNF-alpha and IL-1beta mRNA expression was elevated in the brains of mice with a 1% body weight tumor, relative to the control and CTF groups, without any detectable changes in the other organs. On the other hand, TNF-alpha and IL-1beta mRNA expression was elevated in all organs of mice with an 8% body weight tumor, relative to the control and CTF groups. Tube feeding did not change TNF-alpha and IL-1beta mRNA expression in mice burdened with either a 1% or 8% body weight tumor. CONCLUSIONS: Up-regulation of cytokine mRNA synthesis occurs earlier in the brain than in other organs, and hyperalimentation does not change cytokine mRNA expression in tumor-bearing mice.     

Effects of excess vitamin A and canthaxanthin on salivary gland tumors

The effects of feeding semipurified diets supplemented with excess retinyl palmitate (20,000 and 100,000 IU/kg), beta-carotene (250 mg/kg), and canthaxanthin (250 mg/kg) on 7,12-dimethylbenz[a]anthracene (DMBA)-induced salivary gland tumors were studied in rats. None of the dietary supplements had a significant effect on tumor incidence. Tumor weights, however, tended to be lower in rats fed the dietary supplements compared with the controls. The incidence of tumor-bearing rats with large tumors was significantly lower in rats fed canthaxanthin than in the control rats. At termination of the experiment, the levels of vitamin A were higher in plasma, liver, normal salivary glands, and the tumor of rats fed diets supplemented with the higher level of retinyl palmitate. Feeding the canthaxanthin-supplemented diet had the opposite effect on tissue and plasma vitamin A levels. beta-Carotene supplementation was associated with higher vitamin A concentrations in the liver but not in plasma, salivary glands, or the tumor. The levels of beta-carotene were increased in tissues and plasma of rats fed the beta-carotene-supplemented diet. The results suggest that in this experimental model, the diet-induced modification of tissue or plasma vitamin A levels did not have an effect on tumor incidence.     

Intestinal absorption and excretion of zinc in streptozotocin-diabetic rats as affected by dietary zinc and protein

65Zn was used to examine the effects of dietary zinc and protein on true zinc absorption and intestinal excretion of endogenous zinc by an isotope dilution technique in streptozotocin-diabetic and control rats. Four groups each of diabetic and control rats were fed diets containing 20 ppm Zn, 20% egg white protein (HMHP); 20 ppm Zn, 10% egg white protein (HMLP); 10 ppm Zn, 20% egg white protein (LMHP); and 10 ppm Zn, 10% egg white protein (LMLP). Measurement of zinc balance was begun 9 d after an i.m. injection of 65Zn. True zinc absorption and the contribution of endogenous zinc to fecal zinc excretion were calculated from the isotopically labeled and unlabeled zinc in the feces, duodenum and kidney. Results from the isotope dilution study indicated that diabetic rats, but not control rats, absorbed more zinc from 20 ppm zinc diets than from 10ppm zinc diets and that all rats absorbed more zinc from 20% protein diets than from 10% protein diets. Furthermore, all rats excreted more endogenous zinc from their intestines when dietary zinc and protein levels resulted in greater zinc absorption. In diabetic and control rats, consuming equivalent amounts of zinc, the amount of zinc absorbed was not significantly different, but the amount of zinc excreted by the intestine was less in the diabetic rats. Decreased intestinal excretion of endogenous zinc may be a homeostatic response to the increased urinary excretion of endogenous zinc in the diabetic rats and may also lead to the elevated zinc concentrations observed in some organs of the diabetic rats.     

Metallothionein induction is not involved in cadmium accumulation in the duodenum of mice and rats fed diets containing high-cadmium rice or sunflower kernels and a marginal supply of zinc, iron, and calcium

Rats fed diets with cadmium (Cd) concentrations similar to that found in human diets, and nutritionally marginal with respect to iron (Fe), zinc (Zn), and calcium (Ca) retained 10 times more Cd in the duodenum than rats fed adequate mineral diets. In the current study, 2 experiments were performed to determine the role of intestinal metallothionein (MT) in the accumulation of duodenal Cd, and to determine whether endogenous rice grain Cd is as available as Cd exogenously incorporated into the grain. In Expt. 1, wild-type and MT-null mice were fed 40% rice diets containing marginal or adequate amounts of Fe, Zn, and Ca, and 240 mug Cd/kg. Duodenal Cd was 10 times higher in both wild-type and MT-null mice regardless of their mineral status. In Expt. 2, one group of rats was fed 40% rice diets in which Cd was incorporated into the rice during growth and maturation, and another group was fed 40% rice diets in which Cd was incorporated into the rice during cooking. Each group also was fed either marginal or adequate amounts of Zn, Fe, and Ca. After 5 wk, rats were given a single meal labeled with (109)Cd, and the amount of label retained after 7 d was determined by whole-body counting. Rats with marginal mineral status retained 10 times more (109)Cd than those with adequate status; however, there was no difference between rats fed endogenous or exogenous Cd rice. Although duodenal Cd concentration was 8 times higher in the marginally fed rats, MT concentration was unchanged. These 2 experiments indicate that MT induction is not involved in duodenal Cd accumulation in animals with marginal dietary status of Fe, Zn, and Ca. In addition, they support the hypothesis that marginal deficiencies of Fe, Zn, and Ca, commonly found in certain human populations subsisting on rice-based diets, play an important role in increasing the risk of dietary Cd exposure.     

Interactions of plant zinc and plant species on the bioavailability of plant cadmium to Japanese quail fed lettuce and spinach.

Many cadmium-contaminated environments contain high levels of zinc. The effects of plant Zn and plant species on plant Cd bioavailability were tested in Japanese quail fed lettuce and spinach. Four groups of birds received 10% of their diets as lettuce or spinach leaves intrinsically labeled with 109Cd and containing low or high intrinsic Zn. Two other groups were fed control diets containing 109Cd as CdSO4 and low or high Zn as ZnCO3. Cadmium concentrations in diets ranged from 0.857 to 1.05 micrograms/g dry wt. Zinc concentrations in low-Zn diets ranged from 21.2 to 22.8, and in high-Zn diets from 56.0 to 63.3 micrograms/g dry wt. Increased lettuce and spinach Zn decreased plant Cd retention in kidney, liver, and jejunum-ileum of Japanese quail. Spinach Cd was less absorbed than lettuce Cd at both Zn levels. Inorganic Zn produced a lesser decrease in Cd retention in kidney, liver, and jejunum-ileum than did plant Zn. We conclude that (1) crops that transport Zn and Cd readily into edible tissues show lower Cd bioavailability when grown in Zn-Cd contaminated environments than in Cd-only polluted sites, (2) plant species differ in Cd bioavailability for identical concentrations of Zn and Cd in edible tissues, and (3) toxicological studies with animals exposed to Cd salts and Zn supplements do not assess Cd bioavailability of Zn-Cd contaminated crops.     

Contribution of the cecum and colon to zinc absorption in rats

We examined the role of the large intestine in zinc absorption in rats in three separate experiments. In the first experiment, we examined apparent zinc absorption in rats fed diets containing graded levels of zinc carbonate (0.015-0.535 mmol Zn/kg diet) and evaluated zinc status on the basis of the zinc concentrations in serum and several tissues. The zinc absorption and the serum zinc concentration increased with the zinc content of the diet up to 0. 153 mmol Zn/kg diet. Femoral and pancreatic zinc levels increased linearly up to 0.229 mmol Zn/kg diet. In the second experiment, a zinc carbonate suspension was administered into the cecum via an implanted cannula or into the stomach via an orogastric tube, and the rats were fed diets with or without a highly fermentable fiber, guar gum hydrolysate (GGH, 50 g/kg diet), with coprophagy prevention. The amount of instilled zinc corresponded to the amount of zinc ingested as a component of the diet by the rats of a control group, 0.229 mmol Zn/kg diet. Apparent absorption of cecally instilled zinc was approximately half that observed when zinc was administered into the stomach in both diet groups. Serum and femur zinc concentrations in the cecum-administered groups were approximately 50 and 25% lower, respectively, than those in rats administered zinc into the stomach. The results demonstrate that, in vivo, the absorptive efficiency in the large intestine is not sufficient to satisfy the rat's zinc requirement and does not change when the luminal environment is substantially altered by feeding GGH. In Experiment 3, the effects of cecocolonectomy on zinc absorption were examined in rats with gastric acid suppression. In the cecocolonectomized groups, serum zinc concentration was lower as a result of treatment with a proton pump inhibitor, omeprazole, than in vehicle-treated rats, but not in sham-operated groups. These findings suggest that the cecum and colon contribute to zinc absorption when absorption in the small intestine is impaired.     

Tissue zinc and copper levels in diabetic C57BL/KsJ (db/db) mice fed a zinc-deficient diet: lack of evidence for specific depletion of tissue zinc stores

We investigated whether the decreased femur zinc concentrations reported in genetically obese diabetic db/db C57BL/KsJ mice reflected an increased propensity to zinc deficiency by determining zinc concentrations in tissues from 18-19-wk-old db/db and control mice following ad libitum feeding of a zinc-deficient diet (2 mg/kg) or restricted or ad libitum feeding of a zinc-adequate diet (20 mg/kg) for 12 wk. Although hepatic and renal zinc concentrations of db/db mice fed the zinc-deficient diet tended to be lower than in any other experimental group when expressed on a dry weight basis, zinc concentrations in these tissues were either not different from or greater than those of their nondiabetic controls when expressed on an ash weight basis, i.e., relative to all mineral constituents of these organs. Hepatic and renal copper concentrations of the diabetic db/db mice were either not different from or greater than those of their controls on an ash weight basis. Femur zinc concentrations of diabetic db/db mice fed zinc-adequate diets were lower than those of their controls on a dry weight basis but were not different from their controls on an ash weight basis. We found proportionately lower dry zinc, calcium and magnesium concentrations in femurs of the db/db mice fed a nonpurified diet than in femurs of their db/m and m/m controls. These findings suggest that the low femur zinc concentration reported in the diabetic db/db mouse probably reflects a generalized decrease in bone mineral content rather than a specific depletion of tissue zinc stores.     

Relationship of 65Zn absorption kinetics to intestinal metallothionein in rats: effects of zinc depletion and fasting

Intestinal 65Zn transport and metallothionein levels were examined in rats fed zinc-adequate and zinc-deficient diets and in rats subjected to an overnight fast. 65Zn uptake by intestines perfused with 1.5 microM 65Zn was greater in both zinc-deficient and fasted groups than in the control group. Mucosal retention of 65Zn was also greater in the zinc-deficient group but not in the fasted group. The greater 65Zn uptake in the fasted group was associated with a compartment that readily released 65Zn back into the lumen. Kinetic analysis of the rate of 65Zn transfer to the vascular space (absorption) showed that 65Zn absorption involved approximately 3% of mucosal 65Zn in a 40-min perfusion period. The half-life (t1/2) of this mucosal 65Zn rapid transport pool corresponded directly to changes in intestinal metallothionein levels. Both metallothionein and t1/2 were higher in the fasted group and lower in the zinc-deficient group than in controls. While the rate of 65Zn transport from this rapid transport pool decreased with increasing metallothionein level, the predicted pool size increased when the metallothionein level was elevated by fasting. These results indicate that the rate of zinc absorption is inversely related to intestinal metallothionein levels, but the portion of mucosal 65Zn available for absorption is directly related to intestinal metallothionein.