Showing papers on "Zinc toxicity published in 1999"

The Alzheimer's disease amyloid precursor protein modulates copper-induced toxicity and oxidative stress in primary neuronal cultures.

Abstract: The amyloid precursor protein (APP) of Alzheimer's disease can reduce copper (II) to copper (I) in a cell-free system potentially leading to increased oxidative stress in neurons. We used neuronal cultures derived from APP knock-out (APP(-/-)) and wild-type (WT) mice to examine the role of APP in copper neurotoxicity. WT cortical, cerebellar, and hippocampal neurons were significantly more susceptible than their respective APP(-/-) neurons to toxicity induced by physiological concentrations of copper but not by zinc or iron. There was no difference in copper toxicity between APLP2(-/-) and WT neurons, demonstrating specificity for APP-associated copper toxicity. Copper uptake was the same in WT and APP(-/-) neurons, suggesting APP may interact with copper to induce a localized increase in oxidative stress through copper (I) production. This was supported by significantly higher levels of copper-induced lipid peroxidation in WT neurons. Treatment of neuronal cultures with a peptide corresponding to the human APP copper-binding domain (APP142-166) potentiated copper but not iron or zinc toxicity. Incubation of APP142-166 with low-density lipoprotein (LDL) and copper resulted in significantly increased lipid peroxidation compared to copper and LDL alone. Substitution of the copper coordinating histidine residues with asparagines (APP142-166(H147N, H149N, H151N)) abrogated the toxic effects. A peptide corresponding to the zinc-binding domain (APP181-208) failed to induce copper or zinc toxicity in neuronal cultures. These data support a role for the APP copper-binding domain in APP-mediated copper (I) generation and toxicity in primary neurons, a process that has important implications for Alzheimer's disease and other neurodegenerative disorders.

Uptake and intracellular distribution of labile and total Zn(II) in C6 rat glioma cells investigated with fluorescent probes and atomic absorption.

Abstract: The uptake, intracellular distribution and cytotoxicity of high doses of extracellular zinc was investigated in C6 rat glioma cells. Net zinc uptake occurred only above certain thresholds in time and concentration, below them no alterations of the intracellular zinc level were observed. These results were obtained by measurements with the fluorescent dye Zinquin and by atomic absorption spectrometry, yielding similar results with both methods. Sequestration of zinc in intracellular vesicles was observed by fluorescence microscopy. A protective effect of vesicular sequestration is indicated, because increased levels of intracellular zinc located in vesicles did not necessarily lead to an increase in cytotoxicity. We were able to show that in C6 cells, in contrast to other cell lines, zinc that is released from proteins by the NO donor SNOC is also sequestered in vesicular structures. These zinc-carrying vesicles showed to be constitutive and are assumed to have a function in the maintainance of the cytosolic content of Zn2+ ions.

Regional distribution of metallothionein, zinc, and copper in the brain of different strains of rats.

Abstract: The regional brain distribution of metallothionein (MT), zinc, and copper in the brain was determined in nine anatomical regions (olfactory bulb, cortex, corpus striatum, hippocampus, thalamus plus hypothalamus, pons plus medulla oblongata, cerebellum, midbrain, and white matter) and was compared between two different strains of rat (Sprague-Dawley [SD] and Lewis) No significant difference was observed in the whole-brain MT level between the two strains (178 ± 34 μg/g in SD rats and 203 ± 23 μg/g in Lewis rats) In SD rats, however, MT was more highly expressed in the white matter than in the other regions studied In contrast, MT concentration was highest in the cortex and lowest in the olfactory bulb in Lewis rats The MT levels in the cortex, corpus striatum, hippocampus, and thalamus plus hypothalamus were significantly lower in SD rats than in Lewis rats In both strains, the olfactory bulb contained markedly higher levels of both zinc and copper than the other regions (279 ±68 μg/g zinc in SD rats and 276 ± 69 μg/g zinc in Lewis rats, and 52 ± 15 μg/g copper in SD rats and 111 ± 48 μg/g copper in Lewis rats) The next high-est zinc levels were seen in the hippocampus, whereas the next highest copper levels were in the corpus striatum in both SD and Lewis rats The high levels of zinc and copper in the olfactory bulb were not accompanied by concomitant high MT concentrations These results indicate that the strain of rat as well as the anatomical brain region should be taken into account in MT and metal distribution studies However, the highest concentrations of zinc and copper in olfactory bulb were common to both SD and Lewis rats The discrepancy between MT and the metal levels in olfactory bulb suggests a role for other proteins in addition to MT in the homeostatic control of zinc and copper

Normal and toxic zinc concentrations in serum/plasma and liver of psittacines with respect to genus differences.

Abstract: Determination of zinc concentration in serum/plasma and tissue of caged and aviary birds is commonly requested by practitioners because of an increased awareness of zinc toxicity. However, interpretation of zinc levels is often based on normal zinc concentrations established for poultry. Also, it is likely that intergenus differences exist in normal zinc concentrations of pet birds. In an attempt to determine normal and toxic concentration ranges, zinc concentrations in liver (n = 276) and serum/plasma (n = 260) collected from psittacines between 1990 and 1998 were analyzed. Zinc concentrations were determined by inductively coupled argon plasma emission spectroscopy analysis. The results were categorized by genus and, when available, by history. Birds that were diagnosed with zinc toxicosis (on the basis of history, clinical examination, pathology, and laboratory findings) were exempt and not included in establishing normal ranges. The results indicate that important differences occur with respect to genera. For example, cockatoos and Eclectus parrots have higher normal zinc concentrations in serum or plasma than other psittacines. In addition, analysis of all the submitted cases suggests that potentially toxic zinc concentrations in livers of psittacines can be well below the range considered toxic in chickens (> 200 ppm).

Water pollution studies

Abstract: The acute and chronic toxicity of zinc to feral mottled sculpin (Cottus bairdi) was measured using a 13 day and a 30 day, flow-through toxicity test, respectively. Hardness of exposure water was 48.6 mg/l CaCO3 and 46.3 CaCO3 in the acute and chronic tests, respectively, pH slightly above neutral and temperature near 12°C. The median lethal concentration (LC50) after 96 hours was 156 μg Zn/l, but decreased with duration of exposure to an incipient LC50 of 38 μg Zn/l after 9 days. This was the lowest zinc LC50 reported for any fish species. The incipient LC50 from the 30 d chronic test was was 32 μg Zn/l. The 30 day chronic no-effect and lowest effect concentrations were 16 μg Zn/l (no mortality) and 27 μg Zn/l (32% mortality), respectively. No effects on growth were observed. The results of these tests suggest that mottled sculpin may experience acute and chronic toxicity at zinc concentrations lower than any other fish species tested to date. Protection of aquatic communities in stream reaches contaminated by metals appear to require determination of zinc toxicity to lotic species other than trout. INTRODUCTION Although the toxicity of zinc to fish has been well documented and reviewed (Hogstrand and Wood 1996), the toxicity of this metal is not well known for cold water, littoral species such as sculpin (Cottus spp). Sculpin species inhabit many streams in the western U. S ( Lee et al. 1980), including two species in Colorado (Woodling 1985), the mottled sculpin (Cottus bairdi) and the Paiute sculpin (Cottus beldingi). Sculpin were absent and trout numbers were depressed in a 19.3 km segment of the Eagle River downstream of an inactive mining operation dating to the 1800s near Minturn, Colorado, U.S.A. (unpublished Colorado Division of Wildlife fish monitoring data). At the same time, sculpin were present in the mainstem Eagle River immediately upstream of the mine operation, downstream of the stream reach impacted by mine operation, and in the mouths of three tributaries that enter the mainstem in the 19.3 km metal contaminated reach. Sculpin failed to appear, while brown trout numbers increased, in the 19.3 km reach during the course of a ten year federally mandated restoration program that began in 1988. Zinc was the principal metal of concern through the last half of a ten year period. Based on these observations, Sculpin appeared to be more sensitive to zinc contamination of the Eagle River than trout species. The toxicity of zinc to various trout species has been determined through multiple toxicity tests and incorporated into a US EPA criteria document (USEPA 1987). If sculpin are more sensitive to zinc than trout species, existing criteria and restoration objectives may not be adequate to protect a diverse aquatic community. Determining the relative metal toxicity of variety of native lotic species is required to assure that appropriate water quality criteria and restoration objectives are chosen for stream reaches contaminated by metals. The current study had three objectives. The first objective was to develop a 96h zinc LC50 value for recently hatched wild C. bairdi to assess acute toxicity. The second objective was to conduct a 30 day chronic toxicity test to determine both mortality rates and decreased growth rates of mottled sculpin surviving zinc exposure. Thirdly, results were compared to data for salmonids to determine relative zinc sensitivity. METHODS AND MATERIALS Organisms A total of 134 recently emerged C. bairdi were collected from the White River approximately 5 km east of Meeker, Colorado, U.S.A. on August 8, 2000 for the acute toxicity test using a Smith Root backpack electrofisher unit. Hardness and conductivity at the site of collection was 240 mg/L CaCO3

Influence of glutathione on zinc-mediated cellular toxicity.

Abstract: The effect of zinc on various pulmonary cell lines has been studied by measuring the depletion of total cellular glutathione after exposure to zinc(II) chloride at different concentrations.

The influence of zinc status on the kinetics of zinc uptake into cultured endothelial cells

Abstract: To better understand cellular zinc homeostasis and characterize the zinc transport process, a mammalian cell culture model was utilized to investigate the influence of zinc status on the kinetics of zinc uptake. Culturing conditions were optimized to induce moderate zinc deficiency and zinc excess while still sustaining the general health of the cells. Cells were grown in (1) control medium of 10% fetal bovine serum (FBS) in minimum essential medium (MEM; 5.0 μmol zinc/L), (2) low zinc medium (10% dialyzed FBS in MEM; 1.5 μmol zinc/L), or (3) zinc back medium (10% dialyzed FBS in MEM with zinc added as ZnCl2; 5.0 μmol zinc/L). Bovine pulmonary artery endothelial cells (BPAEC), porcine aortic endothelial cells (PAEC), and porcine venous endothelial cells (PVEC) were evaluated as to their responsiveness to our zinc-deficient conditions. Zinc uptake was faster (P 0.05) between the low zinc group and the control group in the concentration at which uptake was half-maximal (K). Zinc uptake into BPAEC grown in excess zinc conditions was not different (P > 0.05) unless the medium contained greater than 50 μmol zinc/L. In conclusion, BPAEC increased their ability for zinc uptake in response to moderate zinc deficiency, but did not change their kinetics of zinc uptake during moderate zinc excess.

Response of Genotypes of Hyalella azteca to Zinc Toxicity

Abstract: Toxicity tests are most frequently conducted on organisms derived from laboratory cultures that have been reared for many generations following standardized protocols. The restricted density of laboratory populations and the possibility of occasional population crashes increases the probability that random genetic drift and inbreeding may decrease genetic variation of the culture below that typically found in natural populations of the species. Likewise, isolation of organisms in different laboratories may contribute to significant genetic differentiation among culture populations. For example, Duan et al. (1997) present evidence for extensive genetic differentiation among laboratory cultures of the amphipod Hyalella azteca, a species routinely used in toxicity testing. Duan et al. (1997) suggest consistency among toxicity tests performed in different laboratories can only be assured with a knowledge of the genetic similarity among cultures. The recommendation for monitoring the genetic structure of laboratory populations is further supported by the results of studies that indicate, for some species, differential tolerance of genotypes to an environmental stressor (e.g. Sullivan and Lydy 1998, Guttman 1994). In the situation where certain genotypes are more resistant to a particular stressor, using a culture that is dominated by the resistant genotype may underestimate the toxic effect of a contaminant. Similarly, the inclusion of a greater number of sensitive genotypes in a test may overestimate toxicity. This experiment was conducted to test the null hypothesis that no difference in tolerance to zinc contamination would be noted among distinct genotypes of H. azteca obtained from a single laboratory source. Zinc was selected as the contaminant in this study because much of the focus in research conducted to examine genotypic differences in stressor susceptibility has centered on heavy metals. Although zinc is an essential trace element for organisms, it can , at high concentrations, act as an environmental contaminant, particularly in aquatic ecosystems that receive mining effluent. Hyallela azteca was chosen because the research of Duan et al. (1997) indicated genetic differentiation among laboratory cultures and this species is commonly used in ecotoxicological studies.

[Zinc: concepts on an essential micronutrient].

Abstract: It is now well known that zinc is an essential micronutrient. Even though much information is available, there are many points that remain to be studied. zinc is absorbed by the intestine and transported in the plasma by albumin, forming a small exchangeable pool, which is rapidly exhausted even in cases of mild deficiency. zinc is essential for the activity of about 70 enzymes among other functions. Therefore, zinc deficiency produces a great number of clinical disorders, the symptoms of which may range between mild up to serious dysfunctions. These problems are corrected by a dietary supplementation with zinc. The lack of a reliable method to determine the zinc nutritional status reflects the problem to estimate the metal recommended dietary allowances, which are difficulty met specially by children, old persons and pregnant women which constitute the main risk groups. Although our knowledge concerning zinc toxicity is scarce, it is well known that the amounts of zinc that produces toxic effects are much higher than those that are contained in regular diets as well as in diets supplemented with this metal. Therefore, the need of the development of effective strategies, like food fortification with proper zinc compounds, appears as an attractive alternative in order to prevent and/or correct the deficiency of this vital element and to improve the health and the life quality of the whole population.

Tolerance of Some Mediterranean Crops to Copper and Zinc: Implications in Toxic Metal Clean Up

Abstract: A screening of ten different Mediterranean crops was carried out to test their tolerance to soils polluted with copper and zinc. the methods for copper and zinc determination in plants have been improved, avoiding the time consuming acid digestion. Results showed that zinc toxicity was higher than copper for the assayed plants. in copper-polluted soils, Lupinus luteus (lupin) 549 μg g−1 and Zea mays (corn) 213 μg g−1 showed the highest amounts dried weight of accumulated metal, mainly detected associated to the root system without significant reduction of biometrical parameters of the plants. in zinc-contaminated soils, corn (1304 μg g−1), Triticum durum (wheat) (933 μg g−1) and lupin (654 μg g−1) showed the highest amounts of metal accumulated mainly in the roots, and in all cases, without biometrical reduction.

Effect of prior sporidesmin intoxication on the pancreopathy associated with zinc oxide toxicity.

Abstract: Aim. To demonstrate the effect of prior sporidesmin-induced liver injury on the pancreopathy of zinc-induced toxicity. Methods. Four groups, each of 15 sheep, were given 2 × 2 treatments of sporidesmin (0.3 mg/kg bodyweight spread over 3 consecutive days prior to zinc) and zinc (200 mg Zn/kg bodyweight as ZnO spread over 24 days) starting 4 days after the end of sporidesmin dosing. Liver and pancreatic changes were assessed by serum enzyme changes (serum amylase and gamma glutamyltransferase) or scoring for injury at post-mortem examination (hepatopathy) or by histopathological examination (pancreopathy). Results. Minor pancreatic injury was caused by the administration of zinc. The pancreopathy associated with zinc oxide toxicity was significantly greater in those sheep receiving zinc after the sporidesmin-induced injury. Pathological and body weight changes associated with sporidesmin toxicity also occurred in both groups dosed with sporidesmin. These were slightly less in the group of sheep re...

Zinc Chloride Toxicity on Free Proline and Organic Acids in Germinating Rice Seed

Abstract: The study was conducted to find the critical concentrations of zinc toxicity and to determine the changes of the contents of free proline and organic acids with treatment of different zinc chloride concentrations during rice germination and seedlings grown for seven days. The concentration of zinc chloride, 140 ppm, inhibited root elongation as much as 46 times compared with the control, and the germination rate was also decreased in all treatments of zinc chloride, showing that the germination rate decreased more with increasing concentrations of zinc chloride. Its rate was only 13% with treatment of 140 ppm zinc chloride. The content of free proline with treatment of zinc chloride, 140 ppm, was highest about 4,873 M at 3 days compared with the control. Malic acid concentration with treatment of zinc chloride, 140 ppm, increased to approximately 4 times compared to the control. Citric and succinic acid content were also slightly increased in all treatments of zinc chloride.