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15 pages, 1596 KiB

Open AccessArticle

Zn-DTSM, A Zinc Ionophore with Therapeutic Potential for Acrodermatitis Enteropathica?

by Lisa Bray, Irene Volitakis, Scott Ayton, Ashley I. Bush and Paul A. Adlard

Nutrients 2019, 11(1), 206; https://doi.org/10.3390/nu11010206 - 21 Jan 2019

Cited by 1 | Viewed by 6425

Acrodermatitis enteropathica (AE) is a rare disease characterised by a failure in intestinal zinc absorption, which results in a host of symptoms that can ultimately lead to death if left untreated. Current clinical treatment involves life-long high-dose zinc supplements, which can introduce complications [...] Read more.

Acrodermatitis enteropathica (AE) is a rare disease characterised by a failure in intestinal zinc absorption, which results in a host of symptoms that can ultimately lead to death if left untreated. Current clinical treatment involves life-long high-dose zinc supplements, which can introduce complications for overall nutrient balance in the body. Previous studies have therefore explored the pharmacological treatment of AE utilising metal ionophore/transport compounds in an animal model of the disease (conditional knockout (KO) of the zinc transporter, Zip4), with the perspective of finding an alternative to zinc supplementation. In this study we have assessed the utility of a different class of zinc ionophore compound (zinc diethyl bis(N4-methylthiosemicarbazone), Zn-DTSM; Collaborative Medicinal Development, Sausalito, CA, USA) to the one we have previously described (clioquinol), to determine whether it is effective at preventing the stereotypical weight loss present in the animal model of disease. We first utilised an in vitro assay to assess the ionophore capacity of the compound, and then assessed the effect of the compound in three in vivo animal studies (in 1.5-month-old mice at 30 mg/kg/day, and in 5-month old mice at 3 mg/kg/day and 30 mg/kg/day). Our data demonstrate that Zn-DTSM has a pronounced effect on preventing weight loss when administered daily at 30 mg/kg/day; this was apparent in the absence of any added exogenous zinc. This compound had little overall effect on zinc content in various tissues that were assessed, although further characterisation is required to more fully explore the cellular changes underlying the physiological benefit of this compound. These data suggest that Zn-DTSM, or similar compounds, should be further explored as potential therapeutic options for the long-term treatment of AE. Full article

(This article belongs to the Special Issue Health Effects of Dietary Zinc)

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15 pages, 457 KiB

Open AccessArticle

Impact of Two Forms of Daily Preventive Zinc or Therapeutic Zinc Supplementation for Diarrhea on Hair Cortisol Concentrations Among Rural Laotian Children: A Randomized Controlled Trial

by Guy-Marino Hinnouho, Robin M. Bernstein, Maxwell A. Barffour, Charles D. Arnold, K. Ryan Wessells, Kethmany Ratsavong, Bangone Bounheuang, Sengchanh Kounnavong and Sonja Y. Hess

Nutrients 2019, 11(1), 47; https://doi.org/10.3390/nu11010047 - 27 Dec 2018

Cited by 7 | Viewed by 5254

Abstract

Zinc supplementation has been shown to reduce the morbidity burden among young children, and may reduce chronic stress. Hair cortisol has been promoted as an indicator of chronic stress. We assessed the impact of different strategies for delivering supplementary zinc on hair cortisol [...] Read more.

Zinc supplementation has been shown to reduce the morbidity burden among young children, and may reduce chronic stress. Hair cortisol has been promoted as an indicator of chronic stress. We assessed the impact of different strategies for delivering supplementary zinc on hair cortisol concentrations (HCC) in young Laotian children and examined risk factors associated with HCC. In a randomized double-blind controlled trial (NCT02428647), children aged 6–23 mo were randomized to one of four intervention groups and followed for ~36 weeks: daily preventive zinc (PZ) tablets (7 mg/day), daily multiple micronutrient powder (MNP) sachets (containing 10 mg zinc and 14 other micronutrients), therapeutic zinc (TZ) supplements for diarrhea treatment (20 mg/day for 10 days) or daily placebo powder. HCC of 512 children was assessed at baseline and endline. ANCOVA and linear regression models were used to assess group differences in HCC and to examine the risk factors associated with HCC, respectively. At enrollment, mean HCC was 28.8 ± 43.9 pg/mg. In models adjusted for age at enrollment, health district, and baseline HCC there was no overall effect of the interventions on endline HCC and change in HCC. When controlling for additional predetermined covariates, there was a marginally significant effect on change in HCC (p = 0.075) with a slightly lower reduction of HCC in TZ compared to PZ (mean change (95% CI): −4.6 (−7.0; −2.3) vs. −9.4 (−11.7; −7.0) pg/mg; p = 0.053). At baseline, consumption of iron rich foods was negatively associated with HCC, whereas AGP (α1-acid glycoprotein) levels, elevated AGP and C-reactive protein and high soluble transferrin receptor were positively associated with HCC. In young Laotian children, MNP, PZ and TZ had no impact on HCC. The marginal difference in change in HCC between the PZ and TZ groups was too small to be considered of health significance. Full article

(This article belongs to the Special Issue Health Effects of Dietary Zinc)

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14 pages, 513 KiB

Open AccessArticle

Dietary Zinc and Risk of Prostate Cancer in Spain: MCC-Spain Study

by Enrique Gutiérrez-González, Adela Castelló, Pablo Fernández-Navarro, Gemma Castaño-Vinyals, Javier Llorca, Dolores Salas-Trejo, Inmaculada Salcedo-Bellido, Nuria Aragonés, Guillermo Fernández-Tardón, Juan Alguacil, Esther Gracia-Lavedan, Esther García-Esquinas, Inés Gómez-Acebo, Pilar Amiano, Dora Romaguera, Manolis Kogevinas, Marina Pollán and Beatriz Pérez-Gómez

Nutrients 2019, 11(1), 18; https://doi.org/10.3390/nu11010018 - 20 Dec 2018

Cited by 14 | Viewed by 6511

Abstract

Zinc is a key trace element in normal prostate cell metabolism, and is decreased in neoplastic cells. However, the association between dietary zinc and prostate cancer (PC) in epidemiologic studies is a conflicting one. Our aim was to explore this association in an [...] Read more.

Zinc is a key trace element in normal prostate cell metabolism, and is decreased in neoplastic cells. However, the association between dietary zinc and prostate cancer (PC) in epidemiologic studies is a conflicting one. Our aim was to explore this association in an MCC-Spain case-control study, considering tumor aggressiveness and extension, as well as genetic susceptibility to PC. 733 incident cases and 1228 population-based controls were included for this study. Dietary zinc was assessed using a food frequency questionnaire, and genetic susceptibility was assessed with a single nucleotide polymorphisms (SNP)-based polygenic risk score (PRS). The association between zinc intake and PC was evaluated with mixed logistic and multinomial regression models. They showed an increased risk of PC in those with higher intake of zinc (Odds Ratio (OR) tertile 3vs1: 1.39; 95% Confidence interval (CI):1.00–1.95). This association was mainly observed in low grade PC (Gleason = 6 RRR tertile 3vs1: 1.76; 95% CI:1.18–2.63) as well as in localized tumors (cT1-cT2a RRR tertile 3vs1: 1.40; 95% CI:1.00–1.95) and among those with higher PRS (OR tertile 3vs1: 1.50; 95% CI:0.89–2.53). In conclusion, a higher dietary zinc intake could increase the risk of low grade and localized tumors. Men with higher genetic susceptibility might also have a higher risk of PC associated with this nutrient intake. Full article

(This article belongs to the Special Issue Health Effects of Dietary Zinc)

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16 pages, 5594 KiB

Open AccessArticle

Proteomic Analysis of Zn Depletion/Repletion in the Hormone-Secreting Thyroid Follicular Cell Line FRTL-5

by Barbara Guantario, Angela Capolupo, Maria Chiara Monti, Guido Leoni, Giulia Ranaldi, Alessandra Tosco, Liberato Marzullo, Chiara Murgia and Giuditta Perozzi

Nutrients 2018, 10(12), 1981; https://doi.org/10.3390/nu10121981 - 14 Dec 2018

Cited by 3 | Viewed by 3223

Abstract

Zinc deficiency predisposes to a wide spectrum of chronic diseases. The human Zn proteome was predicted to represent about 10% of the total human proteome, reflecting the broad array of metabolic functions in which this micronutrient is known to participate. In the thyroid, [...] Read more.

Zinc deficiency predisposes to a wide spectrum of chronic diseases. The human Zn proteome was predicted to represent about 10% of the total human proteome, reflecting the broad array of metabolic functions in which this micronutrient is known to participate. In the thyroid, Zn was reported to regulate cellular homeostasis, with a yet elusive mechanism. The Fischer Rat Thyroid Cell Line FRTL-5 cell model, derived from a Fischer rat thyroid and displaying a follicular cell phenotype, was used to investigate a possible causal relationship between intracellular Zn levels and thyroid function. A proteomic approach was applied to compare proteins expressed in Zn deficiency, obtained by treating cells with the Zn-specific chelator N,N,N′,N′-tetrakis (2-pyridylmethyl) ethylene-diamine (TPEN), with Zn repleted cells. Quantitative proteomic analysis of whole cell protein extracts was performed using stable isotope dimethyl labelling coupled to nano-ultra performance liquid chromatography-mass spectrometry (UPLC-MS). TPEN treatment led to almost undetectable intracellular Zn, while decreasing thyroglobulin secretion. Subsequent addition of ZnSO₄ fully reversed these phenotypes. Comparative proteomic analysis of Zn depleted/repleted cells identified 108 proteins modulated by either treatment. Biological process enrichment analysis identified functions involved in calcium release and the regulation of translation as the most strongly regulated processes in Zn depleted cells. Full article

(This article belongs to the Special Issue Health Effects of Dietary Zinc)

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19 pages, 823 KiB

Open AccessArticle

The Zinc-Metallothionein Redox System Reduces Oxidative Stress in Retinal Pigment Epithelial Cells

by Sara Rodríguez-Menéndez, Montserrat García, Beatriz Fernández, Lydia Álvarez, Andrés Fernández-Vega-Cueto, Miguel Coca-Prados, Rosario Pereiro and Héctor González-Iglesias

Nutrients 2018, 10(12), 1874; https://doi.org/10.3390/nu10121874 - 02 Dec 2018

Cited by 37 | Viewed by 5314

Abstract

Oxidative stress affects all the structures of the human eye, particularly the retina and its retinal pigment epithelium (RPE). The RPE limits oxidative damage by several protective mechanisms, including the non-enzymatic antioxidant system zinc-metallothionein (Zn-MT). This work aimed to investigate the role of [...] Read more.

Oxidative stress affects all the structures of the human eye, particularly the retina and its retinal pigment epithelium (RPE). The RPE limits oxidative damage by several protective mechanisms, including the non-enzymatic antioxidant system zinc-metallothionein (Zn-MT). This work aimed to investigate the role of Zn-MT in the protection of RPE from the oxidative damage of reactive oxygen intermediates by analytical and biochemical-based techniques. The Zn-MT system was induced in an in vitro model of RPE cells and determined by elemental mass spectrometry with enriched isotopes and mathematical calculations. Induced-oxidative stress was quantified using fluorescent probes. We observed that 25, 50 or 100 μM of zinc induced Zn-MT synthesis (1.6-, 3.6- and 11.9-fold, respectively), while pre-treated cells with zinc (25, 50, and 100 μM) and subsequent 2,2′-Azobis(2-methylpropionamidine) dihydrochloride (AAPH) treatment increased Zn-MT levels in a lesser extent (0.8-, 2.1-, 6.1-fold, respectively), exerting a stoichiometric transition in the Zn-MT complex. Moreover, AAPH treatment decreased MT levels (0.4-fold), while the stoichiometry remained constant or slightly higher when compared to non-treated cells. Convincingly, induction of Zn-MT significantly attenuated oxidative stress produced by free radicals’ generators. We conclude that the stoichiometry of Zn-MT plays an important role in oxidative stress response, related with cellular metal homeostasis. Full article

(This article belongs to the Special Issue Health Effects of Dietary Zinc)

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12 pages, 292 KiB

Open AccessArticle

Fe, Zn and Se Bioavailability in Chicken Meat Emulsions Enriched with Minerals, Hydroxytyrosol and Extra Virgin Olive Oil as Measured by Caco-2 Cell Model

by Lorena Martínez, Gaspar Ros and Gema Nieto

Nutrients 2018, 10(8), 969; https://doi.org/10.3390/nu10080969 - 26 Jul 2018

Cited by 20 | Viewed by 5219

Abstract

There is a high demand for functional meat products due to increasing concern about food and health. In this work, Zn and Se bioavailability was increased in chicken meat emulsions that are enriched with Hydroxytyrosol (HXT), a phenolic compound obtained from olive leaf. [...] Read more.

There is a high demand for functional meat products due to increasing concern about food and health. In this work, Zn and Se bioavailability was increased in chicken meat emulsions that are enriched with Hydroxytyrosol (HXT), a phenolic compound obtained from olive leaf. Six different chicken emulsions were elaborated. Three were made with broiler chicken meat supplemented with inorganic Zn and Se: control, one with HXT (50 ppm) added and one with HXT (50 ppm) and Extra Virgin Olive Oil (EVOO) (9.5%) added; and, three were made with chicken meat from chickens fed a diet that was supplemented with organic Zn and Se: control, one with HXT (50 ppm) added and one with HXT (50 ppm) and EVOO (9.5%) added. The samples were digested in vitro and the percent decomposition of phenolic compounds was measured by HPLC. Mineral availability (Fe, Zn and Se) was measured by cell culture of the Caco-2 cell line and the results were compared with mineral standards (Fe, Zn, and Se). The data obtained showed that neither HXT resistance to digestion nor Fe availability was affected by the presence of organic Zn and Se or phenolic compounds. Zn uptake increased in the presence of HXT, but not when its organic form was used, while Se uptake increased but it was not affected by the presence of HXT. It was concluded that the enrichment of meat—endogenously with organic minerals and exogenously with phenolic compounds—could be considered an interesting strategy for future research and applications in the current meat industry. Full article

(This article belongs to the Special Issue Health Effects of Dietary Zinc)

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9 pages, 780 KiB

Open AccessArticle

Lower Serum Zinc Levels in Patients with Multiple Sclerosis Compared to Healthy Controls

by Marc Pawlitzki, Julia Uebelhör, Catherine M. Sweeney-Reed, Heike Stephanik, Juliane Hoffmann, Anke Lux and Dirk Reinhold

Nutrients 2018, 10(8), 967; https://doi.org/10.3390/nu10080967 - 26 Jul 2018

Cited by 23 | Viewed by 5067

Abstract

Objective: Diminished blood levels of zinc have been reported to be associated with T-cell-mediated autoimmunity, which has been implicated in multiple sclerosis (MS). We aimed to compare the distribution of serum zinc status in MS patients with that in healthy controls (HCs) and [...] Read more.

Objective: Diminished blood levels of zinc have been reported to be associated with T-cell-mediated autoimmunity, which has been implicated in multiple sclerosis (MS). We aimed to compare the distribution of serum zinc status in MS patients with that in healthy controls (HCs) and to investigate a potential correlation with clinical state, through analysis of serum zinc concentration in MS patients suffering from different disease subtypes. Methods: Serum zinc concentrations of 133 patients with relapsing (RMS) and 18 patients with the progressive form of MS (PMS), according to the McDonald criteria of 2010, were measured. Clinical status was quantified using the Expanded Disability Status Scale (EDSS). Zinc concentrations were also determined in the sera of 50 HCs, matched for age and sex at a group level. Results: MS patients showed significantly lower zinc concentrations (mean (SD)) than HCs (12.5 (2.1) µmol/L vs. 14.6 (2.3) µmol/L, p < 0.001). In contrast, we did not find any difference between RMS (12.4 (2.0) µmol/L) and PMS (13.0 (3.0) µmol/L) cases (p = 0.8). Patients receiving disease-modifying treatment showed lower mean (SD) serum zinc levels than untreated cases (12.3 (1.9) µmol/L vs. 13.5 (3.2) µmol/L, p < 0.03). Zinc levels were not related to disease duration, EDSS, annual relapse rate, or the median number of relapses. Conclusions: The data suggest that a diagnosis of MS is related to lower serum zinc concentrations than in HCs, and concentrations were lower still under disease-modifying therapy. However, zinc levels did not predict disease subtypes or disability status. Full article

(This article belongs to the Special Issue Health Effects of Dietary Zinc)

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12 pages, 257 KiB

Open AccessArticle

Association between Dietary Zinc Intake and Hyperuricemia among Adults in the United States

by Yiying Zhang, Yan Liu and Hongbin Qiu

Nutrients 2018, 10(5), 568; https://doi.org/10.3390/nu10050568 - 05 May 2018

Cited by 29 | Viewed by 6186

Abstract

We aim to explore the associations between dietary zinc intake and hyperuricemia (HU) in United States (US) adults. 24,975 US adults aged 20 years or older from the National Health and Nutrition Examination Survey (NHANES) from 2001 to 2014 were stratified into quintiles [...] Read more.

We aim to explore the associations between dietary zinc intake and hyperuricemia (HU) in United States (US) adults. 24,975 US adults aged 20 years or older from the National Health and Nutrition Examination Survey (NHANES) from 2001 to 2014 were stratified into quintiles based on zinc intake. All dietary intake measured through 24-h dietary recalls. Multivariable logistic regression analysis was performed to examine the association between zinc intake and HU after adjustment for possible confounders. For males, compared with respondents consuming less than 7.33 mg zinc daily, the adjusted odds ratios (ORs) were 0.83 (95% CI, 0.71, 0.97) among those consuming 10.26–13.54 mg zinc daily, 0.78 (95% CI, 0.63–0.96) among those consuming 18.50 mg or greater, and p for the trend was 0.0134. For females, compared with respondents consuming less than 5.38 mg zinc daily, the OR was 0.78 (95% CI, 0.63, 0.97) among those consuming 9.64–12.93 mg zinc daily, and p for the trend was 0.3024. Our findings indicated that dietary zinc intake is inversely associated with HU in US men and women, independent of some major confounding factors. Full article

(This article belongs to the Special Issue Health Effects of Dietary Zinc)

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11 pages, 1775 KiB

Open AccessReview

Biotechnological Approaches for Generating Zinc-Enriched Crops to Combat Malnutrition

by Kathleen Hefferon

Nutrients 2019, 11(2), 253; https://doi.org/10.3390/nu11020253 - 23 Jan 2019

Cited by 47 | Viewed by 6670

Abstract

The past twenty years have seen the application of biotechnology to generate nutritionally improved food crops. Biofortified rice, cassava, maize, sorghum and other staple crops biofortified with essential micronutrients have great potential to benefit the world’s poor, in terms of both health and [...] Read more.

The past twenty years have seen the application of biotechnology to generate nutritionally improved food crops. Biofortified rice, cassava, maize, sorghum and other staple crops biofortified with essential micronutrients have great potential to benefit the world’s poor, in terms of both health and economics. This paper describes the use of genetic modification to generate crops that are biofortified with zinc. Examples of zinc-enhanced crops which have been developed using biotechnological approaches will be discussed, and new approaches for research and development will be outlined. The impact of these biofortified crops on human health and well-being will be examined. This paper will conclude with a discussion of the obstacles that must be overcome to enable zinc-fortified crops to be accessible for the world’s malnourished. Full article

(This article belongs to the Special Issue Health Effects of Dietary Zinc)

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