High Doses Of Zinc Research Articles

Effect of zinc supplementation on the distribution of lead in tissues of rats intoxicated by lead compounds

The permissible threshold level of lead in blood (Pb-B) is currently established at 5 mg dL-1, but evidence suggests that it is impossible to determine the safety threshold for lead (Pb) and any exposure, especially in children, must be considered as potentially harmful. Methods used to reduce the concentration of Pb in blood (e.g. EDTA, penicillamine) are not always effective and are associated with serious side effects. One of the proposed dietary supplements in the case of exposure to Pb and low blood Pb concentrations is zinc (Zn), but the published literature on its effectiveness is limited. Therefore, the aim of this study was to clarify whether Zn supplementation may help reduce the concentration of Pb in the blood and tissues of rats, at the Pb-B level previously recognized as safe. Tests were performed on 6-8 week old male Wistar rats. Rats were divided into control and experimental groups: Group C – rats receiving drinking water ad libitum for 4 weeks; Group Pb – rats receiving Pb acetate 0.1% (PbAc) in drinking water ad libitum for 4 weeks; Group Zn – rats receiving ZnCO3 300 mg kg-1 diet for 4 weeks; Group Pb+Zn – rats receiving PbAc in drinking water ad libitum plus 300 mg ZnCO3 kg-1 diet for 4 weeks. The applied dose of 300 mg of ZnCO3 kg-1 diet results in a high but non-toxic Zn level. The concentrations of Pb and Zn in blood, plasma, liver and bone were determined by emission spectrometry in inductively coupled argon plasma (ICP OES). Incidental exposure of adult rats to Pb at doses resulting in the level of Pb in blood below the previously recognized as safe one caused: (i) increased Pb concentration in the bones and plasma and its reduction in the whole blood and liver (ii) simultaneous supplementation of rats exposed to Pb with a high but non-toxic dose of zinc did not result in the reduction of the Pb concentration in the blood and tissues of rats, nor did it induce any changes Irena Baranowska-Bosiacka, Ph.D., Department of Biochemistry and Medical Chemistry, Pomeranian Medical University in Szczecin, Al. Powstancow Wielkopolskich 72, 70-111 Szczecin, Poland, e-mail: ika@univ.szczecin.pl

Enteropathic acrodermatitis in a patient with high-out-put ileostomy

Zinc deficiency is relatively common in certain pathologies, although its clinical manifestation is uncommon. We present the case of a patient who was admitted presenting hyponatremic dehydration and pre-renal failure secondary to high-output ileostomy and oral intolerance. Although the ileostomy output was normalized within 3 days of admission and initial zinc plasma levels were normal, after being fed with TPN supplemented with 13 mg/day of zinc, he suffered a severe zinc deficit with enteropathic acrodermatitis that was completely resolved after one week with 26.5 mg/day. However, plasma levels did not return to normal until one month on therapy with high doses of zinc. Zinc plasma levels are not a good indicator of zinc stores in the body and many times their changes are a late indicator of zinc deficit. There is not a correlation between the clinical improvement and normalization of zinc levels, being common the clinical resolution within few days of the supplementation without observing an increase of zinc plasma levels.

High Dose Zinc Supplementation Induces Hippocampal Zinc Deficiency and Memory Impairment with Inhibition of BDNF Signaling

Zinc ions highly concentrate in hippocampus and play a key role in modulating spatial learning and memory. At a time when dietary fortification and supplementation of zinc have increased the zinc consuming level especially in the youth, the toxicity of zinc overdose on brain function was underestimated. In the present study, weaning ICR mice were given water supplemented with 15 ppm Zn (low dose), 60 ppm Zn (high dose) or normal lab water for 3 months, the behavior and brain zinc homeostasis were tested. Mice fed high dose of zinc showed hippocampus-dependent memory impairment. Unexpectedly, zinc deficiency, but not zinc overload was observed in hippocampus, especially in the mossy fiber-CA3 pyramid synapse. The expression levels of learning and memory related receptors and synaptic proteins such as NMDA-NR2A, NR2B, AMPA-GluR1, PSD-93 and PSD-95 were significantly decreased in hippocampus, with significant loss of dendritic spines. In keeping with these findings, high dose intake of zinc resulted in decreased hippocampal BDNF level and TrkB neurotrophic signaling. At last, increasing the brain zinc level directly by brain zinc injection induced BDNF expression, which was reversed by zinc chelating in vivo. These results indicate that zinc plays an important role in hippocampus-dependent learning and memory and BDNF expression, high dose supplementation of zinc induces specific zinc deficiency in hippocampus, which further impair learning and memory due to decreased availability of synaptic zinc and BDNF deficit.

Alteration in T-Cell Cytokine Production by Vitamin A and Zinc Supplementation in Mice

Simultaneous zinc and vitamin A deficiency are common health problems in developing countries. The objective of this study was to assess effect of supplementation of high zinc or vitamin A on immune function. After three months of feeding with a zinc and vitamin A deficient diet, mice were assigned into four groups which, for additional two months, received a normal or high zinc along with vitamin A deficient diet and a normal or high vitamin A along with zinc deficient diet. Serum and intestinal mucosa immunoglobulin A (IgA) were determined and supernatants of splenocytes were used to assess interlukin (IL)-2, IL-5, IFN-γ. Mice maintained on zinc deficient diet with normal or high vitamin A resulted in significantly lower production of IFN-γ. Also, supplementation of high dose vitamin A augmented production of the cytokine as compared to normal intake of the vitamin. Supplementation of either normal or high zinc along with low vitamin A diet significantly led to higher production of IFN-γ as compared to those receiving zinc limited but adequate vitamin A. High intake of zinc along with vitamin A deficient diet significantly enhanced secretion of IL-2. Levels of serum and mucosal IgA and IL-5 were not be significantly modulated. Moreover, animals fed with high doses of zinc showed increased IL-2 production than those that had normal intake of zinc. Results indicated that zinc and vitamin A supplementation up-regulates production of T-cell cytokines, IFN-γ and IL-2.

Interrelationships between cadmium, zinc and antioxidants in the liver of the rat exposed orally to relatively high doses of cadmium and zinc

Zinc (Zn) reduces cadmium (Cd)-induced toxicity in the liver although it increases Cd tissue burden in some conditions; hence, the present study is designed to study the relationships between Cd, Zn and antioxidants in the liver of rats exposed to Cd. Livers of male rats which received orally relatively high doses of Cd (200 mg Cd/L as Cd chloride or Cd (200 mg/L)+Zn (500 mg Zn as Zn chloride) during five weeks, were investigated. Cd induced an accumulation of Cd and Zn in parallel to depletion in important variables (GSH, GSH/GSSG, CuZn-SOD and GPx activities) and to elevation in others (Cd/Zn and GSSG). Cd, did not affect CuZn SOD/GPx, nor Mn-SOD in the liver. Cd accumulation, Cd/Zn, CuZn SOD activity and CuZn SOD/GPx, was increased remarkably under Zn action. Zn supply ameliorated GSH level and partially reversed the decrease in GSH/GSSG, but it did not ameliorate GPx activity. Analysis showed high correlations between Cd and the majority of the variables, while Zn was positively correlated with only GSSG. We suggest from our results that Zn has indirect ameliorative effects on Cd-induced toxicity in the liver and that the increase in Cd retention is probably the key mechanism modulating, in the case of relatively high doses of Cd, the antioxidant response during exposure to Cd and Zn.

Zinc lozenges may shorten the duration of colds: a systematic review.

Background:A number of controlled trials have examined the effect of zinc lozenges on the common cold but the findings have diverged. The purpose of this study was to examine whether the total daily dose of zinc might explain part of the variation in the results.Methods:The Medline, Scopus and Cochrane Central Register of Controlled Trials data bases were searched for placebocontrolled trials examining the effect of zinc lozenges on common cold duration. Two methods were used for analysis: the P-values of the trials were combined by using the Fisher method and the results of the trials were pooled by using the inverse-variance method. Both approaches were used for all the identified trials and separately for the low zinc dose and the high zinc dose trials.Results:Thirteen placebo-controlled comparisons have examined the therapeutic effect of zinc lozenges on common cold episodes of natural origin. Five of the trials used a total daily zinc dose of less than 75 mg and uniformly found no effect. Three trials used zinc acetate in daily doses of over 75 mg, the pooled result indicating a 42% reduction in the duration of colds (95% CI: 35% to 48%). Five trials used zinc salts other than acetate in daily doses of over 75 mg, the pooled result indicating a 20% reduction in the duration of colds (95% CI: 12% to 28%).Conclusions:This study shows strong evidence that the zinc lozenge effect on common cold duration is heterogeneous so that benefit is observed with high doses of zinc but not with low doses. The effects of zinc lozenges should be further studied to determine the optimal lozenge compositions and treatment strategies.

Zinc Overload Enhances APP Cleavage and Aβ Deposition in the Alzheimer Mouse Brain

BackgroundAbnormal zinc homeostasis is involved in β-amyloid (Aβ) plaque formation and, therefore, the zinc load is a contributing factor in Alzheimer's disease (AD). However, the involvement of zinc in amyloid precursor protein (APP) processing and Aβ deposition has not been well established in AD animal models in vivo.Methodology/Principal FindingsIn the present study, APP and presenilin 1 (PS1) double transgenic mice were treated with a high dose of zinc (20 mg/ml ZnSO4 in drinking water). This zinc treatment increased APP expression, enhanced amyloidogenic APP cleavage and Aβ deposition, and impaired spatial learning and memory in the transgenic mice. We further examined the effects of zinc overload on APP processing in SHSY-5Y cells overexpressing human APPsw. The zinc enhancement of APP expression and cleavage was further confirmed in vitro.Conclusions/SignificanceThe present data indicate that excess zinc exposure could be a risk factor for AD pathological processes, and alteration of zinc homeostasis is a potential strategy for the prevention and treatment of AD.

Toxicidade do zinco em milheto cultivado em Latossolo Vermelho Distrófico

Zinc toxicity causes nutritional disorders specific for millet plants, damaging dry matter production. The objective of this experiment was to evaluate the effects of zinc application on millet dry matter growth, nutrition and production, grown under greenhouse conditions. The experiment was carried out in FCAV / UNESP in pots filled with a 3 dm3 sample of the superficial horizon of a medium textured Red Dystrophic Oxisol, during the period of October to December 2008. Six doses of zinc (0, 15, 30, 60, 120 and 360 mg dm-3), in the form of zinc sulphate, were applied to the soil. The experiment was arranged in a completely randomized design with four replications. 45 days after emergence, the plants were cut and height, diameter of tillers, number of tillers, leaf area and mass and Zn content in shoot dry matter were evaluated. The use of high doses of zinc decreased millet growth and dry matter production, reaching Zn the toxicity levels in the shoots of 451 mg kg-1.

N‐nitrosodimethylamine changes the expression of glutathione S‐transferase in the liver of male mice: The role of antioxidants

The present study investigated the protective effect of gossypol, selenium, zinc, or glutathione (GSH) against dimethylnitrosamine (DMN)-induced hepatotoxicity in the livers of male mice. The expression and the activity of glutathione S-transferase (GST), levels of GSH, and free radicals (malondialdehyde (MDA)), as well as the activity of glutathione reductase were determined after the treatment of mice for seven consecutive days with low or high doses of gossypol, selenium, zinc, or GSH. In experimental groups, DMN was administered as a single dose for 2 h after the repeated dose treatments of mice for seven consecutive days with each antioxidant. DMN reduced the expression and inhibited the activity of GST. However, repeated treatments of mice with low-dose gossypol or high dose of either selenium or GSH followed by a single dose of DMN induced the expression and the activity of GST. In contrast, low-dose treatments of mice with zinc, selenium, or GSH followed by a single dose of DMN reduced the expression and the activity of GST compared to either control or DMN-treated groups. In addition, high-dose treatment with either gossypol or selenium markedly induced the levels of GSH compared to either control or DMN-treated groups. Interestingly, pretreatment of mice with high dose of either gossypol or selenium for seven consecutive days followed by a single dose of DMN decreased the levels of MDA, whereas DMN induced such levels. It is concluded that high dose of either gossypol or selenium is a stronger protector than zinc and GSH in ameliorating the toxic effects of DMN.

In vitro activation of peripheral mononuclear cells by zinc in HIV-infected patients and healthy controls.

Zinc is a mitogen for peripheral blood mononuclear cells (PBMC). The optimal mitogenic concentration was found to be 0.05 mmol/l (327 micrograms/dl), four times higher than physiological serum levels. Maximal proliferation was observed after 6 days. Limited dilution technique revealed a frequency of zinc reactive cells of 1:3467 (median; range 1:1628-1:6235). Cord blood mononuclear cells from four of six healthy children could be stimulated to proliferate by zinc. A normal zinc-induced proliferative response could be demonstrated in all six HIV-infected patients in the Walter-Reed-stage I, in nine of 11 patients in Walter-Reed II and in only two of five patients in Walter-Reed III. In Walter-Reed IV to VI all eight patients showed a weak response to zinc (less than 50% of the healthy day control). Decreased zinc serum levels were found in 10 of 28 patients and in one of 16 controls. There was a significant correlation of a diminished zinc-induced proliferation with lower serum levels of zinc and a reduced proportion of CD4 helper cells in HIV-1-infected men. Because of a suppression of mitogenesis by high dose of zinc an excessive intake of zinc as used by some HIV-1-infected patients can presently not be recommended. The value of zinc-induced proliferation for monitoring HIV-infected patients has still to be established.

High doses of dietary zinc induce cytokines, chemokines, and apoptosis in reproductive tissues during regression

In chickens, high levels of dietary zinc cause molting, and the reproductive system undergoes complete remodeling concomitant to feather replacement. In the present study, the expression profiles of cytokines and chemokines were investigated in the ovary and oviduct of control hens and of hens induced to molt by zinc feeding. The zinc-induced feed-intake suppression, the changes in corticosterone levels, the immune cell populations in the reproductive tract, and the apoptosis of reproductive tissues were analyzed. The expression of mRNAs for interleukin-6 (IL-6), interferon-gamma (IFN-gamma), the avian ortholog of mammalian IL-8 (chCXCLi2), and a chicken MIP-1beta-like chemokine (chCCLi2) in the ovary and of mRNAs for IL-1beta, IL-6, IFN-gamma, transforming growth factor-beta2, chCXCLi2, and chCCLi2 in the oviduct were upregulated significantly during zinc-induced molting. A simultaneous feed-intake reduction was observed with higher expression of cytokines and chemokines. The results of the present investigation also suggested that the upregulation of corticosterone was closely associated with the increased expression of cytokines and chemokines. An increase in apoptosis within reproductive tissue during tissue regression was also noted. We had previously observed the upregulation of these cytokines expression in an earlier study (molting by feed withdrawal). However, the pattern and the level of expression were different among these two methods. These findings indicate that cytokines might be a common mediator of tissue regression during molting induced by diverse methods, although the pattern of induction is different. Thus, a high dose of dietary zinc seems to induce reproductive regression via the upregulation of cytokines and chemokines, the suppression of feed intake, and the increase in serum corticosterone, resulting finally in the apoptosis of reproductive tissues.

Multi‐rule quality control for the age‐related eye disease study

The Age-Related Eye Disease Study (AREDS), sponsored by the National Eye Institute, was designed to study the natural history and risk factors of age-related macular degeneration (AMD) and cataract, and to evaluate the effect of high doses of antioxidants and zinc on eye disease progression. AMD and cataract are leading causes of visual impairment and blindness in the U.S., with frequency of both diseases increasing dramatically after age 65. Participants were randomly chosen to receive antioxidant or placebo tablets. Blood was drawn annually from a subset of patients, and serum concentrations of 17 different nutritional indicators were measured. Because of the complexity of the analytical methods, and possibility of instrument error due to failure of any one of many component parts, several different instruments were used for most analytes. In addition, to assure that the measurement systems were performing adequately across a wide range of concentrations, multiple control pools were monitored with analyte concentrations at low, medium, and high concentrations. We report here the multi-rule quality control system (MRQCS) used during the later part of the trial (AREDS Phase III). This system was designed to monitor systematic error and random within- and among-run error for analytical runs using 1-3 different quality control pools per run and 1-2 measurements of each pool per run. We demonstrate the features of the MRQCS using quality control (QC) data associated with vitamin C measurements. We also provide operating characteristics to demonstrate how the MRQCS responds to increases in systematic and/or random error.

Effect of high dose oral zinc in mice with severe infection with Streptococcus pneumoniae

Zinc is important for normal function of the immune system and inflammation increases the demand for zinc. We hypothesized that high doses of zinc given during acute pneumococcal illness would alter the severity of infection. 24 six-week-old BALB/c mice were anaesthetized and infected intranasally with Streptococcus pneumoniae. Zinc intake was controlled by administering zinc through an intragastric tube. One group was given normal doses (5 microg/d) and the other group high doses of zinc (225 microg/d). We counted the number of bacteria from venous blood at 24 and 48 h, and from heart puncture and nasal wash at 72 h after intranasal challenge. Mice given excess zinc had 2.65 micromol/l, i.e. 25% higher (p= 0.05) mean plasma zinc concentration compared to those given normal amounts. 75% of mice in both groups developed pneumococcal bacteraemia. There were no differences in the numbers of S. pneumoniae colony forming units (CFUs) in blood or nasal wash between the groups. Thus, high doses of zinc did not alter the severity of systemic pneumococcal infection in mice.

New insights about iron bioavailability inhibition by zinc

Objective We measured the effects of lower and higher doses of zinc (Zn) given as an aqueous solution on the bioavailability of iron (Fe). Methods Fourteen healthy subjects received a solution with 0.5 mg of elemental Fe as ferrous sulfate given alone or with 0.59 mg of Zn as zinc sulfate (molar ratio Zn:Fe 1:1). Fourteen days after they received a second solution with 10 mg of Fe given alone or with 11.71 mg of Zn (molar ratio Zn:Fe 1:1). Iron bioavailability was assessed by erythrocyte incorporation of iron radioisotopes 55Fe and 59Fe. Results No significant effect of Zn on Fe bioavailability was observed at lower doses; however, at higher doses Fe bioavailability was inhibited by 56% ( P < 0.001, repeated measures analysis of variance). Conclusion The inhibitory effect of Zn on Fe bioavailability depends on the total amount of both minerals present in the intestinal lumen. This fact should be considered when designing a supplementation program if Fe and Zn are to be provided together.

Effects of Long-term Zinc Supplementation on Plasma Thiol Metabolites and Redox Status in Patients With Age-related Macular Degeneration

To determine the effects of zinc supplementation on plasma thiol metabolites and their redox status in a cohort of patients with age-related macular degeneration (AMD). Randomized clinical trial that evaluated the effects of high doses of zinc and antioxidants on plasma biomarkers of oxidative stress. This was an ancillary study of the Age-Related Eye Disease Study (AREDS). Subjects with AMD were randomized to one of four treatment groups: (1) antioxidants (vitamin C, 500 mg; vitamin E, 400 IU; and beta carotene, 15 mg), (2) zinc (80 mg zinc oxide, 2 mg cupric oxide), (3) antioxidants plus zinc, or (4) placebo. At 20 and 80 months after randomization, blood specimens were collected and analyzed for glutathione (GSH), oxidized glutathione (GSSG), cysteine (Cys), and cystine (CySS). Although zinc supplementation had no apparent effect on plasma thiol/disulfide redox status at the first blood draw, the group of patients receiving zinc supplementation at the second blood draw had significantly less CySS compared with those not receiving zinc (54.9 vs 64.1 microM; P = .01). There was a time-dependent oxidation of the plasma GHS pool and was not affected by zinc supplementation. Because increased CySS level is associated with aging, oxidative stress, and age-related diseases, the apparent prevention of increased CySS by zinc supplementation warrants additional investigation.

The Effects of Zinc on the Olfactory Neuroepithelium and Olfactory Bulbs of the Sprague-Dawley Rat after oral Administration of Zinc-Gluconate Trihydrate

The most frequent causes of upper respiratory infections are human rhinoviruses. The nasopharyngeal area, which includes the respiratory epithelium, mucosa, and the olfactory neuroepithelium (ONe), is a first-line of defense against airborne viruses and allergens, some of which manage to penetrate the nasal mucosa and invade the tissues of the nasal respiratory epithelium. Biochemical evidence from several studies suggests that zinc is an effective cold treatment and that over-the-counter (OTC) zinc-gluconate compounds may provide the high pharmacologic doses of zinc needed to act as an effective means of treating and reducing the duration and severity of symptoms of the common cold. A series of male Sprague-Dawley rats were fed an oral preparation of zinc-gluconate trihydrate or received the equivalent through drinking water to investigate the potential cytotoxic and/or neurotoxic insult to the olfactory receptor cells and other tissue in the ONe and afferent neuronal pathways. Coronal sections of the rat ONe and corresponding olfactory bulbs showed consistent cellular and tissue damage of increasing severity that correlated with the duration of treatment with the zinc compound when compared with the control group animals. The results of this analysis indicate that the repeated oral administration of such zinc-containing compounds have neurotoxic effects on the ONe and to the mitral cells in the olfactory bulbs of treated rats. These findings point toward the need for increased investigation into the potential deleterious effects of zinc-containing compounds to humans as well.

Acrodermatitis Enteropathica: Zinc Therapy and Possible Identification of a Carrier State Through Multiple Hair Zinc Analyses over Three Decades

We report on the successful use of repeated hair analyses over three decades to monitor zinc and copper status in two siblings with Acrodermatitis enteropathica who were treated with oral zinc sulfate beginning in 1975. Furthermore, we report for the first time that analysis of zinc in hair over a 30-yr period allows for the identification of individuals who might be heterozygous carriers of this autosomal recessive disease and who, therefore, would be expected to have hair zinc levels intermediate between normal, healthy individuals and those with Acrodermatitis enteropathica. Zinc treatment of the two patients with Acrodermatitis enteropathica resulted in remission of the signs and symptoms of the disease within the first month of therapy. However, any short-term interruption (typically, 7-10 d) in oral zinc resulted in an almost immediate relapse, with the reappearance of the skin lesions. We also document the inverse relationship that exists between zinc and copper through analysis of these metals in the scalp hair from the two patients, thus providing a tool for ensuring adequate copper intake in patients taking relatively high doses of zinc over a long period.

Apoptosis ofSpodoptera litura larval hemocytes induced by heavy metal zinc

By adding different amount of zinc into the artificial medium of the insect larvae, the zinc-induced apoptosis of the larvae haemocytes of the herbivorous insectSpodoptera litura Fabricius was investigated with flow cytometer. The results showed that the increase of zinc dose in the artificial feed led to the accumulations of zinc in the larval hemolymph and fat body, and more zinc was accumulated in fat body than in hemolymph. The apoptosis of hemocytes was significantly induced at high zinc concentration (1000 mg·kg−1) in the insect diet, and the apoptosis rate was 63.63%, which was remarkably higher than that at control and lower concentrations (50-500 mg·kg−1). This suggests that the high dose of zinc in the artificial diet ofS. litura larvae could induce the apoptosis of the larval hemocytes ofS. litura.

Zinc as an ambivalent but potent modulator of murine hair growth in vivo– preliminary observations

Oral zinc (Zn(2+)) is often employed for treating hair loss, even in the absence of zinc deficiency, although its mechanisms of action and efficacy are still obscure. In the current study, we explored the in vivo effects of oral zinc using the C57BL/6 mouse model for hair research. Specifically, we investigated whether continuous administration of high-dose ZnSO(4) x 7H(2)O (20 mg/ml) in drinking water affects hair follicle (HF) cycling, whether it retards or inhibits chemotherapy-induced alopecia (CIA) and whether it modulates the subsequent hair re-growth pattern. Here, we show that high doses of oral zinc significantly inhibit hair growth by retardation of anagen development. However, oral zinc also significantly retards and prolongs spontaneous, apoptosis-driven HF regression (catagen). Oral zinc can also retard, but not prevent, the onset of CIA in mice. Interestingly, Zn(2+) treatment of cyclophosphamide-damaged HFs also significantly accelerates the re-growth of normally pigmented hair shafts, which reflects a promotion of HF recovery. However, if given for a more extended time period, zinc actually retards hair re-growth. Thus, high-dose oral zinc is a powerful, yet ambivalent hair growth modulator in mice, whose ultimate effects on the HF greatly depend on the timing and duration of zinc administration. The current study also encourages one to explore whether oral zinc can mitigate chemotherapy-induced hair loss in humans and/or can stimulate hair re-growth.

Zinc-induced anti-apoptotic effects in SH-SY5Y neuroblastoma cells via the extracellular signal-regulated kinase 1/2

Zinc levels are increased in brain areas severely affected by Alzheimer's disease (AD) pathologies. Zinc has both protective and neurotoxic properties and can stimulate both phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways. Several kinases related to these pathways including protein kinase B (PKB), p70 S6 kinase (p70S6K), and extracellular signal-regulated kinase 1/2 (ERK1/2) are known cell survival factors and are overactivated in neurons bearing neurofibrillary tangles (NFTs) in AD. The present study aimed to determine whether anti-apoptotic effects of zinc are mediated via these signaling pathways. Zinc was used to treat SH-SY5Y neuroblastoma cells and effects investigated in relation to PKB, p70S6K, and ERK1/2 in the absence and presence of the pro-apoptotic agent staurosporine (STS). Cell damage was evaluated by measuring levels of DNA fragmentation as well as the WST-1 assay for cell viability. Results indicated that: (1) treatment with high doses of zinc (≥400 μM) for short time periods (≤2 h) gave rise to increased levels of DNA fragments, increased cell membrane permeability, and reduced mitochondria membrane potential; (2) treatment with 100 μM zinc for >2 h reversed an increased DNA fragmentation due to U0126 inhibition of ERK1/2; (3) increased DNA fragmentation due to STS could be protected against by 100 μM zinc; (4) the protective effects of 100 μM zinc on STS-induced DNA fragmentation could be partially reversed by U0126. These results indicate that a zinc-induced anti-apoptotic response in SH-SY5Y cells likely occurs through ERK1/2.