Elevated Zinc Research Articles

Metallothionein Concentrations and Organ Retention of Mercury in the Liver and Kidney of the Neonatal Guinea Pig after Exposure to Mercury Vapor.

Neonatal guinea pigs were exposed to mercury vapor on the day of birth, and the following mercury distribution and concentrations of metallothioneins (MTs) in the liver and kidney were observed. In the liver, two hours after exposure, an appreciable amount of mercury accumulated and a substantial portion of this was associated with MTs. During postnatal development, the mercury concentration increased, whereas the hepatic concentration of MTs decreased. The mercury in the soluble fraction of the liver shifted from the region of MTs to the high-molecular-weight region and, finally, the mercury peak in the MT region was not detected. The kidney mercury concentration was high even 2 hr after the exposure and on days 3 and 7 postpartum. The peak concentration was observed on day 3 postpartum. The mean renal concentration of MTs in the mercury-exposed neonates was significantly higher than that of the control at all times observed. The changes in both the mercury level and the concentration of MTs were strongly correlated. Furthermore, most mercury in the soluble fraction was associated with MTs on day 7. These findings indicated enhanced synthesis of MTs in the kidney, but not in the liver, after mercury vapor exposure in the neonatal period, with corresponding elevated copper and zinc concentrations in the kidney.

Evidence of structural and functional adaptation in epilithon exposed to zinc

Artificial streams were used to study the effect of chronic zinc dosing (0.00,0.05 or 1.00 mg Zn 1- ') on epilithic communities during summer and early fall, 1984 and 1985. Following zinc addition, epilithon was periodically measured for '4C-glucose and 14C-glutamate respiration, ash-free dry weight (AFDW), protein, carbohydrate, chlorophyll a (Chl a), pheophytin a (pheo a), and colony forming units (CFU) on zinc amended and unamended media. Transient peaks in glucose respiration rates mg- ' protein and AFDW occurred within 5 to 10 days in streams dosed with 1.0 mg Zn 1- ' and coincided with decreases in AFDW, protein, carbohydrate, Chl a, and pheo a. Respiration of glutamate did not show a significant response to dosing (a = 0.05). Epilithic plate counts demonstrated more total and zinc-tolerant CFU in dosed than in control epilithon after 20 days. After 30 days, greater biomass and lower protein: carbohydrate ratios were evident in epilithon dosed with 1.0 mg Zn 1- ' compared to unamended treatments. Peaks in glucose respiration suggested the presence of zinc-tolerant heterotrophs transiently capable of increased respiration of glucose but not glutamate. Concurrently, minimal but measurable biomass inferred the persistence of zinc-tolerant microorganisms in zinc-dosed epilithon. By the end of the studies, results indicated that metal-tolerant populations replaced metal-sensitive organisms under conditions of elevated zinc concentration. These zinc adapted communities had lower potential value as a food source to grazers (low protein: carbohydrate ratio) and were no longer distinctive with respect to glucose respiration.

Distribution of trace element pollutants in a contaminated grassland ecosystem established on metalliferous fluorspar tailings. 2: Zinc

Concentrations of zinc in vegetation, invertebrates and small mammals in a grassland ecosystem derived from a mine waste vegetation scheme indicated the high concentration of zinc in the original tailings. However, the considerable differences in soil and vegetation zinc concentrations between the tailings and an uncontaminated site were not reflected in the invertebrate and small mammal communities. Invertebrate zinc levels and total body concentrations in Microtus agrestis L. (field vole) and Sorex araneus L. (common shrew) suggested a notable buffering of zinc absorption and tissue accumulation in the presence of substantially elevated dietary zinc. In the small mammals the skeleton appeared to function as the major storage site for zinc, possibly contributing to homeostasis in the soft tissues.

Elevated serum zinc levels in metal fume fever

Metal fume fever is not an uncommon syndrome among welders following exposure to oxidized metal fumes (usually zinc). The relationship of serum zinc level to the acute phase of this illness is not known. Two cases of metal fume fever, associated with elevated serum zinc levels, are presented. Further studies are necessary to determine the diagnostic usefulness of serum zinc levels in metal fume lever.

Zinc balance in combined zinc deficiency and uremia

In order to evaluate whether the hypozincemia associated with chronic renal failure represents true negative zinc balance, male Lewis rats were randomized and pair-fed zinc replete (+Zn) or deplete (-Zn) diets. Subsequently, each animal underwent one- and two-thirds nephrectomy, or a sham operation. Complete balances for zinc, calcium, and magnesium were determined weekly before and after nephrectomy. At sacrifice, -Zn animals had significantly lower (P less than 0.005) plasma zinc levels compared to controls. Nephrectomized (N) animals had significantly elevated plasma creatinine (P less than 0.005), diminished creatinine clearances (P less than 0.005), and increased urinary flows (P less than 0.005) and protein excretion (P less than 0.01) compared to sham-operated (S) controls. Zinc nutritional status had no effect on these parameters in animals with comparable renal function. -Zn/N animals had consistently significantly elevated (P less than 0.005) urinary zinc excretion compared with -Zn/S with similar plasma zinc concentrations. Urinary zinc excretion correlated with urinary flow (r = 0.739, P less than 0.005), urinary protein (r = 0.635, P less than 0.01) and urinary calcium excretion (r = 0.855, P less than 0.005) in -Zn groups. -Zn/N rats had a significantly larger fecal zinc excretion for the first week post-nephrectomy, compared to -Zn/N controls (P less than 0.005). This resulted in negative zinc balance in -Zn/N animals, compared to their pre-nephrectomy balance (P less than 0.05) or to -Zn/S controls for the first (P less than 0.005) and second (P less than 0.05) weeks. -Zn/N rats had lower (P less than 0.02) hepatic zinc concentrations compared to the -Zn/S group.(ABSTRACT TRUNCATED AT 250 WORDS)

Mercury contribution to an adirondack lake

Elevated copper, lead, and zinc concentrations in the upper 10 to 20 cm of sediment sampled from Cranberry Lake, a large Adirondack lake, are attributed to atmospheric contributions. Pb-210 and pollen core data, however, suggest Cranberry Lake also received mercury discharges during the turn of the century when the area was the center of extensive lumbering and related activities. Elevated mercury concentrations in Cranberry Lake smallmouth bass derived from remobilization from mercury-contaminated bottom sediments which increased the bioavailability to Cranberry Lake organisms. Mercury remobilization and accumulation by fish are promoted by fluctuating pH values resulting from acid precipilation.

Amygdalar kindling is associated with elevated zinc concentration in the cortex and hippocampus of rats

The reported convulsant properties of zinc and its association with hippocampal function prompted investigation of zinc levels during the induction and maintenance of kindling. Rats were fed zinc adequate diets during kindling, incited by daily amygdalar stimulation. The concentration of zinc in hippocampus was unperturbed during 3 stages of kindling induction when compared to either naive, sham surgery, or electroshock controls. In contrast, cortical zinc increased during kindling induction but returned to control levels in fully kindled animals. Two weeks after full kindling was established, the concentration of zinc in the hippocampus and overlying cortex increased significantly, in the absence of further electrical stimulation. The effect was restricted to the central nervous system inasmuch as zinc levels were unaffected in liver and other extracerebral tissues. Moreover, the zinc concentration was relatively unchanged during the 24 h period following a single electroconvulsive seizure, implying that the observed changes were not simply a postictal phenomenon. The results of this study suggest that long-lasting elevations in zinc are present after kindling is established. Whether this finding is related to the perpetuation of abnormal neuronal excitability or represents a compensatory response remains to be elucidated.

Quantification of hippocampal noradrenaline and zinc changes after selective cell destruction.

Deafferentation of septo-hippocampal projections results in sprouting of sympathetic noradrenergic (NA) fibers into the hippocampus. To determine whether dentate granule cells are necessary for the initiation and/or direction of this sprouting, both NA intensity and zinc density were microspectrophotometrically quantified at 10 or 30 days after selective neurotoxin lesions of either granule cells or CA3 pyramidal cells, and electrolytic lesions of medial septum. Groups with elevated zinc density at 10 days also had significantly higher NA levels at 30 days. Destruction of granule cells eliminated the rise in zinc and prevented the NA increase. The zinc increase may be related to a nerve growth factor-like protein responsible for the initiation of sympathetic sprouting.

Altered zinc status of soldiers under field conditions ,

Thirty men were studied during a 34-day intensive training exercise conducted by the U.S. Army. All soldiers were followed to determine the effect of such training, designed to simulate wartime operations, on selected zinc parameters. The soldiers consumed a nutritionally adequate diet made from fresh foods (A rations) prepared at the training site. Dietary intake, weight change, serum zinc, alkaline phosphatase activity, and urinary zinc excretion were measured. The 34-day intensive training exercise was associated with weight loss, depressed serum zinc levels, and elevated urinary zinc excretion. Alkaline phosphatase activity was not altered by the training exercise. The depressed serum zinc concentration could not be explained by the parameters measured. Weight loss was positively correlated with urinary zinc excretion. The functional significance of a depressed serum zinc concentration on performance deserves further study.

METAL REGULATION AND MOLTING IN THE BLUE CRAB,CALLINECTES SAPIDUS:COPPER, ZINC, AND METALLOTHIONEIN

Blue crab, Caiinectes sapidus, hemolymph and digestive glands were examined at differentstagesofthe molt cycle to determine whether molting affectedtissue and cytosolic partitioning of copper and zinc and, if so, whether metallothionein was involved. The crabs used in these determinations were not exposed to elevated con centrations ofcopper or zinc. Concentrations ofhemocyanin, copper, and zinc in the hemolymph all decreased significantly during molt. They were lowest at the soft crab stage (A2) and highest during premolt(D1—D3) and intermolt(C4). The digestive gland copper concentrations also were highest during premolt (D1-D3) and lowest in the papershellstage(B1).Zinc followed the same generalpatternin both hemolymph and digestive glands. The cytosolic distributions of copper and zinc were determined in the digestive glands using gel filtrationchromotography.The elution profilesshowed that the percentagesofcopper and zinc on metallothionein rangedfrom 10%copper/ 90%zinc at D1 to 100%copper at B1. The estimated concentrations of metallothi onein were highestduringintermolt (C1)and premolt (D1-D3) and lowest duringthe papershell(B1).The observedchanges in the tissue and cytosolic partitioningof cop per and zinc are consistent with the physiological changes occurring in the crabs. These observations support the hypothesis that metallothioneins are naturally occur ringproteinsthat are actively involved in the synthesis of hemocyanin and zinc regu lation duringthe normal processesof growthin blue crabs.

Zinc in multiple sclerosis. II: Correlation with disease activity and elevated plasma membrane-bound zinc in erythrocytes from patients with multiple sclerosis.

Previous studies have shown that zinc levels in erythrocytes are significantly elevated in patients with multiple sclerosis (MS). To examine the correlation between erythrocyte Zn levels and disease activity, we measured erythrocyte Zn levels longitudinally. Levels were dramatically decreased during a clinically documented exacerbation of MS. To determine the localization of increased Zn levels in MS erythrocytes, we employed standard techniques for the isolation of nonhemoglobin erythrocyte membrane ghosts. Patients with MS had three times more Zn in ghost material than did controls. Chloroform-methanol extraction in erythrocyte ghosts followed by determination of Zn levels indicated that most of the membrane-bound Zn was associated with the lipid-soluble fraction. Non-lipid-associated Zn and total membrane protein concentration were similar in MS and control samples. Results suggest that mechanisms which govern cellular availability, compartmentalization of Zn, or the binding of Zn to cell surface membranes may be altered in patients with MS, and that these mechanisms vary with disease activity.

The effects of zinc on germination, survival and growth of Betula seed

The effects of increasing zinc concentration on germination, survival and growth of birch seed collected from sites showing varying degrees of zinc contamination were investigated. Germination decreased with elevated zinc levels but differences between different seedlots were not found. Distinct differences were found for percentage survival and growth. Radicle elongation was more adversely affected than hypocotyl extension. The nutrient status of the culture media influenced the toxicity of zinc. Tolerance indices at different developmental stages are compared.

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 10 ppm 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.

Association between urinary zinc excretion and lymphocyte dysfunction in patients with lung cancer

Patients with bronchogenic carcinoma often have low serum zinc concentrations and sometimes have markedly elevated renal zinc losses. Since normal zinc metabolism is critical for the proper function of T lymphocytes and natural killer cells, the effect of zinc status on T cell phytohemagglutinin response and peripheral blood lymphocyte natural killer cell activity was studied in patients with lung cancer. Mean (± SEM) serum zinc concentration in 75 patients with cancer was 67.4 ± 2.2 μg/dl versus 96.0 ± 8.0 μg/dl for normal subjects. Patients with low serum zinc levels (less than 70 μg/dl) had significantly higher urine zinc excretion than patients with normal serum zinc levels (1,385 ± 240 μg per 24 hours versus 392 ± 107 μg per 24 hours) (p <0.001). This pattern of zinc concentrations (i.e., low serum zinc in combination with high urine zinc) is typical of patients with mild zinc deficiency, and suggests that a mild chronic zinc deficiency state was present in some of these patients. When lymphocyte data were analyzed according to serum zinc concentrations and urinary zinc excretion, low serum zinc concentration and high urine zinc excretion both correlated with depressed T cell phytohemagglutinin response (p <0.005 and p <0.001, respectively). For instance, mean maximal phytohemagglutinin response in patients with urinary zinc excretion of more than 700 μg per 24 hours was 22,132 ± 3,201 cpm (n = 14) compared with 68,130 ± 6,850 cpm for patients with normal zinc excretion (n = 7). Peripheral blood lymphocyte natural killer cell activity did not correlate with either serum or urine zinc values. Oral zinc sulfate (220 mg, three times daily for six weeks) was then administered to patients with hyperzincuria (mean = 992 μg per 24 hours). Zinc-supplemented patients had normalization of T cell phytohemagglutinin response after zinc therapy, whereas control patients demonstrated continued T cell dysfunction. Natural killer cell activity did not change in either group during the study period. These data suggest that a mild subclinical zinc deficiency state may exist in some patients with lung cancer and may be an important cause of abnormal T cell function. Furthermore, zinc supplementation may be useful to improve lymphocyte function in selected patients. Whether zinc supplementation would alter the course of the disease or the patient's prognosis is presently unknown.

Zinc and α-fetoprotein in amniotic fluid from early pregnancies with fetal malformations

Zinc and α-fetoprotein concentrations were quantitated in second-trimester amniotic fluid from 111 normal pregnancies and 29 pregnancies with various fetal malformations. The zinc level varied between 0.3 and 4.0 μmol/L (median 1.3) in the normal samples and between 1.8 and 17.9 μmol/L (median 5.0) in cases with malformations. The level was above 2.5 times the normal median in 23 of the 29 (79%) gestations with the malformations. Amniotic fluid zinc and α-fetoprotein levels showed a positive correlation (r = 0.78), and the α-fetoprotein level was elevated in all gestations with fetal disorders and elevated zinc levels, as well as in five of the six cases with fetal defects but normal zinc concentrations. The elevation of zinc was more marked than that of α-fetoprotein in three cases of fetal malformations. Five samples were false positive on α-fetoprotein assay but contained normal zinc levels. Removal of α-fetoprotein from amniotic fluid had no effect on the zinc concentration, indicating that zinc is not bound to amniotic fluid α-fetoprotein.

Zinc deficiency and the developing embryo

The effect ofin utero zinc deficiency on fetal development in rats is reviewed. Attention is paid to the primary biochemical lesion associated with zinc-related teratogenesis and special consideration is given to the central nervous system. Evidence is presented that the thymidine kinase salvage pathway, used for the synthesis of thymidine monophosphate in DNA synthesis, is depressed more in fetal brain tissue than in the liver. In addition, greater reliance appears to be placed on this pathway than onde novo synthesis in the fetal brain than in other tissues. Some consideration is given to the use of in vitro embryo culture in studies relating to neurogenesis, but evidence is presented of a greater capacity of explanted rat embryos to obtain zinc from maternal serum than occurs in vivo.The rapid onset of a teratogenic zinc deficiency following dietary zinc restriction is again highlighted and further studies are described which demonstrate the critical impact of a single feeding cycle, of 4 d duration, on maternal plasma zinc levels and on the extent and nature of the observed fetal abnormalities. Evidence is presented that by shifting the timing of the high dietary intake/low plasma zinc peak to coincide with a particular 48 h period between days 6 and 10 of pregnancy, the pattern of malformations thus obtained reflected the coincidence of the high dietary intake of zinc-deficient diet and the critical time of morphogenesis of several organ systems.Whereas diminished plasma zinc levels at term in zinc-deficient animals are generally well correlated with reduced growth and dysmorphogenesis of the offspring, the same is not always found in human studies. In some cases, elevated plasma zinc levels at parturition are found in mothers with growth-retarded children, or vice versa. Experimental studies with rats are reported that suggest that maternal zinc status at term may be higher in dams bearing pups stunted by exposure to a transient zinc deficiency early in pregnancy, which in turn may have reduced the demand for maternal zinc in the later stages of gestation.The protective effect of zinc on cadmium-induced teratogenesis is discussed, particularly in relation to findings concerning an interaction of these metals in the embryonic yolk sac and thus on preplacental embryonic nutrition. Possible interactions between alcohol and zinc deficiency are also considered and data are presented pointing to increased fetotoxicity and teratogenesis in the presence of both treatments and to a more specific interaction with respect to reduced cell numbers in the developing rat hippocampus. Malondialdehyde levels, which reflect the extent of lipid peroxidation in tissue, are reported to be substantially higher in microsomes from fetal rat livers whenin utero deficiency and gestational alcoholism are combined. The suggestion is made that alcohol and zinc deficiency act independently in the body, but overlap to some extent at the common biochemical locus of membrane lipid peroxidation.

Evaluation of amniotic fluid zinc levels in open neural tube defects

SummaryAmniotic fluid zinc concentration (mean 1·6±0·5μmol/L) in 131 pregnancies without fetal abnormalities in the second trimester did not increase with gestation. An elevated mean zinc level, 6·8±2·5 μmol/L, was detected in seven amniotic fluids with anencephalic fetuses. In amniotic fluids from 20 cases of fetal open spina bifida, a mean zinc concentration of 2·8±1.5 μmol/L was also significantly elevated but there was only elevation (>2 s.d.) in 40 per cent of these 20 cases of open spina bifida. Amniotic fluid zinc measurements are not suitable to complement α-fetoprotein estimations for the detection of open neural defects. There were no normal fetuses with elevated zinc amniotic fluid concentrations but in 6 out of 8 with fetal malformations other than neural tube defects, amniotic fluid zinc values were raised. Contamination with maternal blood resulted in falsely elevated zinc concentrations in 52 per cent of contaminated amniotic fluids.

Cellular metal distribution in the Pacific oyster, Crassostrea gigas (Thun.) determined by quantitative X-ray microprobe analysis

Tissues of Pacific oysters, Crassostrea gigas (Thun.), from the metal-rich Derwent Estuary, Tasmania, were examined using electron microscopy and the cellular metal concentrations measured by X-ray microanalysis. These data showed that 1. (1) all tissues contained elevated copper and zinc concentrations when compared with other bivalves (e.g. Mytilus), 2. (2) with the exception of reproductive tissues, calcium, iron, copper and zinc were present in the tertiary lysosomes, 3. (3) copper and zinc were selectively accumulated in membrane-limited vesicles of blood amoebocytes to cellular concentrations of ≈ 70 mM Cu and 390 mM Zn and 4. (4) these amoebocytes contain > 90% of the body copper and zinc.

Zinc and acute tropical ulcers in Gambian children and adolescents

28 Gambian children and adolescents with acute tropical leg ulcers entered a double blind trial of oral zinc supplements as an adjunct to standard treatment. Analysis of the area healing of the ulcers resulted in a mathematical expression which showed that for each subject re-epithelialization reduced the ulcer radius at a constant healing rate (k). k was derived from the equation At = pi X (r - k X t)2, where At = residual ulcer area at time "t", r = initial ulcer radius and t = time from start of treatment. In the zinc treated group k was 0.55 +/- 0.39 mm/day, and 0.51 +/- 0.25 mm/day in the placebo group. The initial low plasma zinc of 6.5 +/- 1.9 mumol/L in the ulcerated subjects was not significantly lower than that of 7.5 +/- 3.6 mumol/L in the nonulcerated controls. Oral zinc supplements significantly elevated plasma zinc concentrations by 5.8 +/- 4.8 mumol/L compared to the placebo group's change of 0.4 +/- 2.0 mumol/L (p less than 0.001). Plasma alkaline phosphatase activities and fatty acid profiles did not change with zinc supplementation. Thus unequivocal clinical and biochemical evidence of zinc deficiency in these ulcerated subjects was not established, despite changes in plasma zinc. This study does not indicate any role for zinc supplementation in the management of acute tropical ulcers.

Immunohistochemical demonstration of the cytoplasmic copper-associated protein in the liver in primary biliary cirrhosis: its identification as metallothionein.

Metallothionein was isolated from the liver of rats pretreated with cadmium. Monospecific anti-metallothionein antibodies were produced in rabbits. Twenty-six primary biliary cirrhosis (PBC) liver samples and three control liver samples were stained for metallothionein by an indirect immunoperoxidase technique. Nineteen of the PBC samples and the control samples were also stained for copper by Timm's silver sulphide method. In all PBC samples the copper concentration was determined. In addition, the zinc, cadmium, and mercury concentrations were measured in some samples. Eighteen of the PBC samples stained for metallothionein showed marked diffuse cytoplasmic and nuclear staining of a varying number of periportal hepatocytes. In none of them was granular staining detected. None of the control samples showed staining. Fourteen of the PBC samples stained for copper showed diffuse cytoplasmic and granular staining of the periportal hepatocytes. In none of them was nuclear staining detected. None of the control samples showed staining. No elevated zinc, cadmium, or mercury concentrations were found but the copper concentration was increased in 21 of the 26 PBC samples. The number of cells staining for copper and metallothionein was assessed semiquantitatively. Significant correlations were found between the grade of metallothionein staining and the liver copper concentration; the grade of Timm's staining and the liver copper concentration; and the grades of metallothionein staining and Timm's staining. The data suggest that the accumulation of copper induces synthesis of cytoplasmic and nuclear metallothionein, and that the increased amount of cytoplasmic copper is bound to a similarly increased amount of metallothionein.