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The Mechanisms of Zinc Action as a Potent Anti-Viral Agent: The Clinical Therapeutic Implication in COVID-19. Antioxidants (Basel) 2022; 11:antiox11101862. [PMID: 36290585 PMCID: PMC9598180 DOI: 10.3390/antiox11101862] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Revised: 09/14/2022] [Accepted: 09/16/2022] [Indexed: 11/17/2022] Open
Abstract
The pandemic of COVID-19 was caused by a novel coronavirus termed as SARS-CoV2 and is still ongoing with high morbidity and mortality rates in the whole world. The pathogenesis of COVID-19 is highly linked with over-active immune and inflammatory responses, leading to activated cytokine storm, which contribute to ARDS with worsen outcome. Currently, there is no effective therapeutic drug for the treatment of COVID-19. Zinc is known to act as an immune modulator, which plays an important role in immune defense system. Recently, zinc has been widely considered as an anti-inflammatory and anti-oxidant agent. Accumulating numbers of studies have revealed that zinc plays an important role in antiviral immunity in several viral infections. Several early clinical trials clearly indicate that zinc treatment remarkably decreased the severity of the upper respiratory infection of rhinovirus in humans. Currently, zinc has been used for the therapeutic intervention of COVID-19 in many different clinical trials. Several clinical studies reveal that zinc treatment using a combination of HCQ and zinc pronouncedly reduced symptom score and the rates of hospital admission and mortality in COVID-19 patients. These data support that zinc might act as an anti-viral agent in the addition to its anti-inflammatory and anti-oxidant properties for the adjuvant therapeutic intervention of COVID-19.
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Shalini R, Jeyasekaran G, Shakila RJ, Sundhar S, Arisekar U, Jawahar P, Aanand S, Sivaraman B, Malini AH, Surya T. Dietary intake of trace elements from commercially important fish and shellfish of Thoothukudi along the southeast coast of India and implications for human health risk assessment. MARINE POLLUTION BULLETIN 2021; 173:113020. [PMID: 34649206 DOI: 10.1016/j.marpolbul.2021.113020] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Revised: 09/20/2021] [Accepted: 09/29/2021] [Indexed: 06/13/2023]
Abstract
The concentrations of eight trace elements (chromium, cobalt, copper, zinc, arsenic, cadmium, mercury and lead) in14 commercially important fish and shellfish collected from Thoothukudi along the southeast coast of India was investigated using inductively coupled plasma mass spectrometry in order to assess the health risks associated with their consumption. The concentration of trace elements ranged from 0.001 to 39.5 μg/g. The estimated weekly intake of cadmium in seven fish and shellfish (0.0081-0.0996 mg/kg body weight) were above the provisional tolerable weekly intake set by the Joint FAO/WHO Expert Committee on Food Additives. The risk assessment analysis indicated that there was non- carcinogenic risk upon lifetime consumption of rock crab, C. natator (TTHQ >1) and carcinogenic risks upon lifetime consumption of S. jello, P. semisulcatus, P. sanguinolentus C. natator, Uroteuthis duvaceli, Sepia pharaonis and Cistopus indicus due to cadmium exposure indicating a potential health risk to the exposed consumers.
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Affiliation(s)
- Rajendran Shalini
- Department of Fish Quality Assurance and Management, Fisheries College and Research Institute, Thoothukudi, India
| | | | - Robinson Jeya Shakila
- Department of Fish Quality Assurance and Management, Fisheries College and Research Institute, Thoothukudi, India
| | - Shanmugam Sundhar
- Department of Fish Quality Assurance and Management, Fisheries College and Research Institute, Thoothukudi, India
| | - Ulaganathan Arisekar
- Department of Fish Quality Assurance and Management, Fisheries College and Research Institute, Thoothukudi, India
| | - Paulraj Jawahar
- Tamil Nadu Dr. J. Jayalalithaa Fisheries University, Nagapattinam, India
| | - Samraj Aanand
- Erode Centre for Sustainable Aquaculture, Erode, India
| | - Balasubramanian Sivaraman
- Department of Fish Quality Assurance and Management, Fisheries College and Research Institute, Thoothukudi, India
| | - Asha Hema Malini
- Department of Fish Quality Assurance and Management, Fisheries College and Research Institute, Thoothukudi, India
| | - Tamizhselvan Surya
- Department of Fish Quality Assurance and Management, Fisheries College and Research Institute, Thoothukudi, India
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Davis J, Umeh U, Saba R. Treatment of SARS-CoV-2 (COVID-19): A safety perspective. World J Pharmacol 2021; 10:1-32. [DOI: 10.5497/wjp.v10.i1.1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2021] [Revised: 08/22/2021] [Accepted: 09/17/2021] [Indexed: 02/06/2023] Open
Abstract
The goal of this review is to report a balanced perspective of current evidence for efficacy of treatments for coronavirus disease 2019 (COVID-19) against the historical safety of these treatments as of May 2021. We preselected therapies of interest for COVID-19 based on national guidelines and modified over time. We searched PubMed and Medline for these specific COVID-19 treatments and data related to their efficacy. We also searched for prior randomized controlled trials of each therapy to assess adverse effects, and we obtained the Food and Drug Administration Approval label for this information. Several drugs have been approved for the treatment of COVID-19, and many more are under study. This includes dexamethasone, remdesivir, hydroxychloroquine/chloroquine, lopinvir/ritonavir, interferon or interleukin inhibitors, convalescent plasma and several vitamins and minerals. The strongest evidence for benefit is mortality benefit with dexamethasone in patients with COVID-19 and hypoxemia, although there is a signal of harm if this is started too early. There are several other promising therapies, like interleukin inhibitors and ivermectin. Hydroxychloroquine/chloroquine, lopinvir/ritonavir, and convalescent plasma do not have enough evidence of benefit to outweigh the known risks of these drugs.
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Affiliation(s)
- Joshua Davis
- Department of Emergency Medicine, Vituity, Wichita, KS 67214, United States
| | - Ugochukwu Umeh
- College of Medicine, Medical University of Lublin, Lublin 20-093, Poland
| | - Rand Saba
- Department of Surgery, Ascension Providence Hospital, Southfield, MI 48075, United States
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Pal A, Squitti R, Picozza M, Pawar A, Rongioletti M, Dutta AK, Sahoo S, Goswami K, Sharma P, Prasad R. Zinc and COVID-19: Basis of Current Clinical Trials. Biol Trace Elem Res 2021; 199:2882-2892. [PMID: 33094446 PMCID: PMC7580816 DOI: 10.1007/s12011-020-02437-9] [Citation(s) in RCA: 86] [Impact Index Per Article: 21.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2020] [Accepted: 10/11/2020] [Indexed: 12/13/2022]
Abstract
Coronavirus disease-2019 (COVID-19) pandemic continues to threaten patients, societies, and economic and healthcare systems around the world. Like many other diseases, the host immune system determines the progress of COVID-19 and fatality. Modulation of inflammatory response and cytokine production using immunonutrition is a novel concept that has been applied to other diseases as well. Zinc, one of the anti-inflammatory and antioxidant micronutrient found in food with well-established role in immunity, is currently being used in some clinical trials against COVID-19. This review integrates the contemporary studies of role of zinc in antiviral immunity along with discussing its potential role against COVID-19, and ongoing COVID-19 clinical trials using zinc.
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Affiliation(s)
- Amit Pal
- Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), Kalyani, West Bengal, 741245, India.
| | - Rosanna Squitti
- Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy
| | - Mario Picozza
- Neuroimmunology Unit, IRCSS Fondazione Santa Lucia, 00143, Rome, Italy
| | - Anil Pawar
- Department of Zoology, DAV University, Jalandhar, Punjab, India
| | - Mauro Rongioletti
- Department of Laboratory Medicine, Research and Development Division, San Giovanni Calibita Fatebenefratelli Hospital, Isola Tiberina, Rome, Italy
| | - Atanu Kumar Dutta
- Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), Kalyani, West Bengal, 741245, India
| | - Sibasish Sahoo
- Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), Kalyani, West Bengal, 741245, India
| | - Kalyan Goswami
- Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), Kalyani, West Bengal, 741245, India
| | - Praveen Sharma
- Department of Biochemistry, AIIMS, Jodhpur, Rajasthan, India
| | - Rajendra Prasad
- Department of Biochemistry, MM Institute of Medical Sciences and Research, Mullana, Ambala 133207, Haryana, India
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Evaluation of 28-day repeated oral dose toxicity of SUNACTIVE Zn-P240 in rats. Regul Toxicol Pharmacol 2021; 125:105001. [PMID: 34242707 DOI: 10.1016/j.yrtph.2021.105001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Revised: 06/27/2021] [Accepted: 07/05/2021] [Indexed: 11/23/2022]
Abstract
This study was conducted to investigate the potential toxicity of repeated oral dose of SUNACTIVE Zn-P240, a new type of zinc supplement, in Sprague-Dawley rats. SUNACTIVE Zn-P240 was administered once daily by gavage at doses of 0, 500, 1000, and 2000 mg/kg/day for each group over a 28-day period. At 2000 mg/kg/day, there were increases in serum alkaline phosphatase (ALP) and alanine aminotransferase, liver weight, histopathological changes in stomach, liver, and pancreas and decreases in body weight, food consumption, hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration, total protein (TP), and albumin. At 1000 mg/kg/day, there was an increase in the serum ALP level and there were decreases in the MCV, MCH, and TP. There were no treatment-related adverse effects in the 500 mg/kg/day group. Under the present experimental conditions, the target organs in rats were determined to be the stomach, pancreas, liver, and erythrocyte and the no-observed-adverse-effect level (NOAEL) in rats was considered to be 500 mg/kg/day.
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Asl SH, Nikfarjam S, Majidi Zolbanin N, Nassiri R, Jafari R. Immunopharmacological perspective on zinc in SARS-CoV-2 infection. Int Immunopharmacol 2021; 96:107630. [PMID: 33882442 PMCID: PMC8015651 DOI: 10.1016/j.intimp.2021.107630] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2020] [Revised: 03/30/2021] [Accepted: 03/30/2021] [Indexed: 02/06/2023]
Abstract
The novel SARS-CoV-2 which was first reported in China is the cause of infection known as COVID-19. In comparison with other coronaviruses such as SARS-CoV and MERS, the mortality rate of SARS-CoV-2 is lower but the transmissibility is higher. Immune dysregulation is the most common feature of the immunopathogenesis of COVID-19 that leads to hyperinflammation. Micronutrients such as zinc are essential for normal immune function. According to the assessment of WHO, approximately one-third of the world's society suffer from zinc deficiency. Low plasma levels of zinc are associated with abnormal immune system functions such as impaired chemotaxis of polymorphonuclear cells (PMNs) and phagocytosis, dysregulated intracellular killing, overexpression of the inflammatory cytokines, lymphopenia, decreased antibody production, and sensitivity to microbes especially viral respiratory infections. Zinc exerts numerous direct and indirect effects against a wide variety of viral species particularly RNA viruses. The use of zinc and a combination of zinc-pyrithione at low concentrations impede SARS-CoV replication in vitro. Accordingly, zinc can inhibit the elongation step of RNA transcription. Furthermore, zinc might improve antiviral immunity by up-regulation of IFNα through JAK/STAT1 signaling pathway in leukocytes. On the other hand, zinc supplementation might ameliorate tissue damage caused by mechanical ventilation in critical COVID-19 patients. Finally, zinc might be used in combination with antiviral medications for the management of COVID-19 patients. In the current review article, we review and discuss the immunobiological roles and antiviral properties as well as the therapeutic application of zinc in SARS-CoV-2 and related coronaviruses infections.
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Affiliation(s)
- Sima Heydarzadeh Asl
- Cellular and Molecular Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran.
| | - Sepideh Nikfarjam
- Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Naime Majidi Zolbanin
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Urmia University of Medical Sciences, Urmia, Iran.
| | - Reza Nassiri
- Departments of Pharmacology and Community Medicine, Michigan State University, East Lansing, MI, USA.
| | - Reza Jafari
- Solid Tumor Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran.
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Hernández-Moreno D, Li L, Connolly M, Conde E, Fernández M, Schuster M, Navas JM, Fernández-Cruz ML. Mechanisms underlying the enhancement of toxicity caused by the coincubation of zinc oxide and copper nanoparticles in a fish hepatoma cell line. ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY 2016; 35:2562-2570. [PMID: 26970269 DOI: 10.1002/etc.3425] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/13/2015] [Revised: 01/07/2016] [Accepted: 03/07/2016] [Indexed: 06/05/2023]
Abstract
Ecosystems are exposed to a wide variety of individual substances, including at the nano-scale; and the potential adverse effects of their interactions are an increasing concern. The purpose of the present study was to determine whether zinc oxide nanoparticles (ZnONPs) at a no-observed-effect concentration modulate the cytotoxicity of copper nanoparticles (CuNPs) in the fish hepatoma cell line PLHC-1 after 48 h of exposure and the contribution of the released ions to these effects. Cells were exposed to 50-nm CuNPs (0.39-25.0 µg/mL), alone or in combination with ZnONPs (25 nm or 100 nm), at 6.25 µg/mL. Cells were exposed to suspensions of NPs or to their supernatants, as well as to their combinations. The effects on cell viability were assessed through cytotoxicity assays. Changes in cell morphology and metal internalization were also evaluated. The cytotoxicity exerted by CuNPs was enhanced in the presence of nontoxic concentrations of ZnONPs. On the contrary, Zn ions protected the cell line from the CuNP toxicity, this effect being related to an increase in the intracellular levels of Zn. This increase of metal was not observed in cells exposed to both ZnONPs and CuNPs, even when they were visualized inside the cell. The results indicated that the internalization of ZnONPs, but not the Zn ions, was responsible for the enhanced toxicity of the CuNPs. Environ Toxicol Chem 2016;35:2562-2570. © 2016 SETAC.
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Affiliation(s)
- David Hernández-Moreno
- Environment Department, Spanish Institute for Agricultural and Food Research and Technology (INIA), Madrid, Spain
| | - Lingxiangyu Li
- State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China
| | - Mona Connolly
- Environment Department, Spanish Institute for Agricultural and Food Research and Technology (INIA), Madrid, Spain
| | - Estefania Conde
- Centre for Energy, Environmental and Technological Research (CIEMAT), Madrid, Spain
| | - Marta Fernández
- Centre for Energy, Environmental and Technological Research (CIEMAT), Madrid, Spain
| | - Michael Schuster
- Department of Chemistry, Technische Universität München, Garching, Germany
| | - José Maria Navas
- Environment Department, Spanish Institute for Agricultural and Food Research and Technology (INIA), Madrid, Spain
| | - María-Luisa Fernández-Cruz
- Environment Department, Spanish Institute for Agricultural and Food Research and Technology (INIA), Madrid, Spain.
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Roney N, Osier M, Paikoff SJ, Smith CV, Williams M, De Rosa CT. ATSDR evaluation of the health effects of zinc and relevance to public health. Toxicol Ind Health 2016; 22:423-93. [PMID: 17533814 DOI: 10.1177/0748233706074173] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
As part of its mandate, the Agency for Toxic Substances and Disease Registry (ATSDR) prepares toxicological profiles on hazardous chemicals found at Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) National Priorities List (NPL) sites, which have the greatest public health impact. These profiles comprehensively summarise toxicological and environmental information. This article constitutes the release of portions of the Toxicological Profile for Zinc. The primary purpose of this article is to provide public health officials, physicians, toxicologists, and other interested individuals and groups with an overall perspective on the toxicology of zinc. It contains descriptions and evaluations of toxicological studies and epidemiological investigations, and provides conclusions, where possible, on the relevance of toxicity and toxicokinetic data to public health. Toxicology and Industrial Health 2006; 22: 423-493.
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Affiliation(s)
- Nickolette Roney
- Agency for Toxic Substances and Disease Registry (ATSDR), US Department of Health and Human Services, Atlanta, GA, USA
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Liu Z, Wu X, Zhang T, Guo J, Gao X, Yang F, Xing X. Effects of Dietary Copper and Zinc Supplementation on Growth Performance, Tissue Mineral Retention, Antioxidant Status, and Fur Quality in Growing-Furring Blue Foxes (Alopex lagopus). Biol Trace Elem Res 2015; 168:401-10. [PMID: 26032444 DOI: 10.1007/s12011-015-0376-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2015] [Accepted: 05/19/2015] [Indexed: 11/24/2022]
Abstract
A 4×2 factorial experiment with four supplemental levels of copper (0, 20, 40, or 60 mg copper per kg dry matter) from copper sulfate and two supplemental levels of zinc (40 or 200 mg zinc per kg dry matter) from zinc sulfate was conducted to investigate the effects of dietary copper and zinc supplementation on growth performance, tissue mineral retention, antioxidant status, and fur quality in growing-furring blue foxes. One hundred and twenty healthy 15-week-old male blue foxes were randomly allocated to eight dietary treatments with 15 replicates per treatment for a 70-day trial from mid-September to pelting in December. The average daily gain and feed conversion ratio were increased with copper supplementation in the first 35 days as well as the overall period (P<0.05). In addition, copper supplementation tended to increase feed intake during the first 35 days (P<0.10). Diets supplemented with 200 mg/kg zinc did not affect body gain (P>0.10) and feed intake (P>0.10) but improved feed conversion (P<0.05) compared with those supplemented 40 mg/kg zinc throughout the experiment. No copper×zinc interaction was observed for growth performance except that a tendency (P=0.09) was found for feed intake in the first 35 days. Supplementation of copper or zinc improved crude fat digestibility (P<0.01) but had no effects on the digestibility of other nutrients. Fecal copper was increased with both copper (P<0.01) and zinc addition (P<0.05). However, fecal zinc was affected only by dietary zinc addition (P<0.01). Mineral contents in serum and kidney were not affected by dietary treatments (P>0.05). However, the level of copper in the liver was increased with copper supplementation (P<0.05) and tended to decrease with zinc supplementation (P=0.08). Dietary zinc addition tended to increase the activity of alkaline phosphatase (P=0.07). The activities of copper-zinc superoxide dismutase and catalase tended to increase by copper (P=0.08) and zinc addition (P=0.05). Moreover, a copper×zinc interaction was observed for catalase in the experiment (P<0.05). Serum malondialdehyde concentration decreased with the increasing of dietary copper and zinc levels (P<0.05). The activity of glutathione peroxidase tended to increase by copper addition (P=0.09). For fur quality, foxes fed diets supplemented with high copper had larger skin length and darker pelts than those fed the basal diet without copper addition (P<0.05). In conclusion, this study demonstrated that dietary copper and zinc supplementation can improve growth by increasing feed intake and improving fat digestibility. Additionally, copper and zinc can enhance the antioxidant capacity of blue foxes. This study also indicates that additional zinc up to 200 mg/kg did not exert significant adverse effects on the copper metabolism of growing-furring blue foxes.
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Affiliation(s)
- Zhi Liu
- Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing, 100081, China.
- State Key Lab for Molecular Biology of Special Economic Animals, Changchun City, Jilin, 130112, China.
| | - Xuezhuang Wu
- Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing, 100081, China
| | - Tietao Zhang
- Institute of Special Wild Economic Animals and Plants, Chinese Academy of Agricultural Sciences, Changchun City, Jilin, 130112, China
- State Key Lab for Molecular Biology of Special Economic Animals, Changchun City, Jilin, 130112, China
| | - Jungang Guo
- Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing, 100081, China
| | - Xiuhua Gao
- Feed Research Institute, Chinese Academy of Agricultural Sciences, Beijing, 100081, China.
| | - Fuhe Yang
- Institute of Special Wild Economic Animals and Plants, Chinese Academy of Agricultural Sciences, Changchun City, Jilin, 130112, China
- State Key Lab for Molecular Biology of Special Economic Animals, Changchun City, Jilin, 130112, China
| | - Xiumei Xing
- Institute of Special Wild Economic Animals and Plants, Chinese Academy of Agricultural Sciences, Changchun City, Jilin, 130112, China
- State Key Lab for Molecular Biology of Special Economic Animals, Changchun City, Jilin, 130112, China
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Wu J, Wang L, He J, Zhu C. In vitro cytotoxicity of Cu2+, Zn2+, Ag+ and their mixtures on primary human endometrial epithelial cells. Contraception 2012; 85:509-18. [DOI: 10.1016/j.contraception.2011.09.016] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2011] [Revised: 09/15/2011] [Accepted: 09/29/2011] [Indexed: 11/28/2022]
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Brocard A, Dréno B. Innate immunity: a crucial target for zinc in the treatment of inflammatory dermatosis. J Eur Acad Dermatol Venereol 2011; 25:1146-52. [DOI: 10.1111/j.1468-3083.2010.03934.x] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
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Plum LM, Rink L, Haase H. The essential toxin: impact of zinc on human health. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2010; 7:1342-65. [PMID: 20617034 PMCID: PMC2872358 DOI: 10.3390/ijerph7041342] [Citation(s) in RCA: 764] [Impact Index Per Article: 50.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/27/2010] [Revised: 03/08/2010] [Accepted: 03/10/2010] [Indexed: 12/13/2022]
Abstract
Compared to several other metal ions with similar chemical properties, zinc is relatively harmless. Only exposure to high doses has toxic effects, making acute zinc intoxication a rare event. In addition to acute intoxication, long-term, high-dose zinc supplementation interferes with the uptake of copper. Hence, many of its toxic effects are in fact due to copper deficiency. While systemic homeostasis and efficient regulatory mechanisms on the cellular level generally prevent the uptake of cytotoxic doses of exogenous zinc, endogenous zinc plays a significant role in cytotoxic events in single cells. Here, zinc influences apoptosis by acting on several molecular regulators of programmed cell death, including caspases and proteins from the Bcl and Bax families. One organ where zinc is prominently involved in cell death is the brain, and cytotoxicity in consequence of ischemia or trauma involves the accumulation of free zinc. Rather than being a toxic metal ion, zinc is an essential trace element. Whereas intoxication by excessive exposure is rare, zinc deficiency is widespread and has a detrimental impact on growth, neuronal development, and immunity, and in severe cases its consequences are lethal. Zinc deficiency caused by malnutrition and foods with low bioavailability, aging, certain diseases, or deregulated homeostasis is a far more common risk to human health than intoxication.
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Affiliation(s)
- Laura M Plum
- Institute of Immunology, Medical Faculty, RWTH Aachen University, Pauwelstrasse 30, 52074 Aachen, Germany.
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Kirchgessner M, Reichlmayr-Lais AM, Mathur AK. Fe-, Cu- und Mn-Konzentration in ausgewählten Organen und Geweben von Ratten nach unterschiedlicher Zn- und Ni-Versorgung. ACTA ACUST UNITED AC 2009. [DOI: 10.1111/j.1439-0396.1985.tb00025.x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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Rincker MJ, Hill GM, Link JE, Meyer AM, Rowntree JE. Effects of dietary zinc and iron supplementation on mineral excretion, body composition, and mineral status of nursery pigs1,2. J Anim Sci 2005; 83:2762-74. [PMID: 16282614 DOI: 10.2527/2005.83122762x] [Citation(s) in RCA: 56] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Two experiments were conducted to evaluate the effects of dietary Zn and Fe supplementation on mineral excretion, body composition, and mineral status of nursery pigs. In Exp. 1 (n = 24; 6.5 kg; 16 to 20 d of age) and 2 (n = 24; 7.2 kg; 19 to 21 d of age), littermate crossbred barrows were weaned and allotted randomly by BW, within litter, to dietary treatments and housed individually in stainless steel pens. In Exp. 1, Phases 1 (d 0 to 7) and 2 (d 7 to 14) diets (as-fed basis) were: 1) NC (negative control, no added Zn source); 2) ZnO (NC + 2,000 mg/kg as Zn oxide); and 3) ZnM (NC + 2,000 mg/kg as Zn Met). In Exp. 2, diets for each phase (Phase 1 = d 0 to 7; Phase 2 = d 7 to 21; Phase 3 = d 21 to 35) were the basal diet supplemented with 0, 25, 50, 100, and 150 mg/kg Fe (as-fed basis) as ferrous sulfate. Orts, feces, and urine were collected daily in Exp. 1; whereas pigs had a 4-d adjustment period followed by a 3-d total collection period (Period 1 = d 5 to 7; Period 2 = d 12 to 14; Period 3 = d 26 to 28) during each phase in Exp. 2. Blood samples were obtained from pigs on d 0, 7, and 14 in Exp. 1 and d 0, 7, 21, and 35 in Exp. 2 to determine hemoglobin (Hb), hematocrit (Hct), and plasma Cu, (PCu), Fe (PFe), and Zn (PZn). Pigs in Exp. 1 were killed at d 14 (mean BW = 8.7 kg) to determine whole-body, liver, and kidney mineral concentrations. There were no differences in growth performance in Exp. 1 or 2. In Exp. 1, pigs fed ZnO or ZnM diets had greater (P < 0.001) dietary Zn intake during the 14-d study and greater fecal Zn excretion during Phase 2 compared with pigs fed the NC diet. Pigs fed 2,000 mg/kg, regardless of Zn source, had greater (P < 0.010) PZn on d 7 and 14 than pigs fed the NC diet. Whole-body Zn, liver Fe and Zn, and kidney Cu concentrations were greater (P < 0.010), whereas kidney Fe and Zn concentrations were less (P < 0.010) in pigs fed pharmacological Zn diets than pigs fed the NC diet. In Exp. 2, dietary Fe supplementation tended to increase (linear, P = 0.075) dietary DMI, resulting in a linear increase (P < 0.050) in dietary Fe, Cu, Mg, Mn, P, and Zn intake. Subsequently, a linear increase (P < 0.010) in fecal Fe and Zn excretion was observed. Increasing dietary Fe resulted in a linear increase in Hb, Hct, and PFe on d 21 (P < 0.050) and 35 (P < 0.010). Results suggest that dietary Zn or Fe additions increase mineral status of nursery pigs. Once tissue mineral stores are loaded, dietary minerals in excess of the body's requirement are excreted.
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Affiliation(s)
- M J Rincker
- Department of Animal Science, Michigan State University, East Lansing, 48824, USA
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Persia ME, Parsons CM, Baker DH. Amelioration of oral copper toxicity in chicks by dietary additions of ascorbic acid, cysteine and zinc. Nutr Res 2003. [DOI: 10.1016/j.nutres.2003.08.013] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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18
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Pohl HR, Roney N, Wilbur S, Hansen H, De Rosa CT. Six interaction profiles for simple mixtures. CHEMOSPHERE 2003; 53:183-197. [PMID: 12892681 DOI: 10.1016/s0045-6535(03)00436-3] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/24/2023]
Abstract
The Agency for Toxic Substances and Disease Registry (ATSDR) has a program for chemical mixtures that encompasses research on chemical mixtures toxicity, health risk assessment, and development of innovative computational methods. ATSDR prepared a guidance document that instructs users on how to conduct health risk assessment on chemical mixtures (Guidance Manual for the Assessment of Joint Toxic Action of Chemical Mixtures). ATSDR also developed six interaction profiles for chemical mixtures. Two profiles were developed for persistent environmental chemicals that are often found in contaminated fish and also can be detected in human breast milk. The mixture included chlorinated dibenzo-p-dioxins, hexachlorobenzene, dichlorodiphenyl dichloroethane, methyl mercury, and polychlorinated biphenyls. Two profiles each were developed for mixtures of metals and mixtures of volatile organic chemicals (VOCs) that are frequently found at hazardous waste sites. The two metal profiles dealt with (a) lead, manganese, zinc, and copper; and (b) arsenic, cadmium, chromium, and lead; the two VOCs mixtures dealt with (a) 1,1,1-trichloroethane, 1,1-dichloroethane, trichloroethylene, and tetrachloroethylene; and (b) benzene, ethylbenzene, toluene, and xylenes (BTEX). Weight-of-evidence methodology was used to assess the joint toxic action for most of the mixtures. Physiologically based pharmacokinetic modeling was used for BTEX. In most cases, a target-organ toxicity dose modification of the hazard index approach is recommended for conducting exposure-based assessments of noncancer health hazards.
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Affiliation(s)
- Hana R Pohl
- Agency for Toxic Substances and Disease Registry, US Department of Health and Human Services, 1600 Clifton Road, Atlanta, Georgia 30333, USA.
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19
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The influence of dietary microbial phytase and copper on copper status in growing pigs. Anim Feed Sci Technol 2003. [DOI: 10.1016/s0377-8401(03)00007-5] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
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20
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Influence of chronic zinc supplementation on biochemical variables and circadian rhythms in Wistar rats. Nutr Res 2000. [DOI: 10.1016/s0271-5317(00)00134-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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21
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Baker DH. Cupric oxide should not be used as a copper supplement for either animals or humans. J Nutr 1999; 129:2278-9. [PMID: 10573563 DOI: 10.1093/jn/129.12.2278] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Affiliation(s)
- D H Baker
- Department of Animal Sciences and Division of Nutritional Sciences, University of Illinois, Urbana, IL 61801, USA
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22
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Bhathena SJ, Werman MJ, Turnlund JR. Opioid Peptides, Adrenocorticotrophic Hormone and Dietary Copper Intake in Humans. Nutr Neurosci 1998; 1:59-67. [PMID: 27405911 DOI: 10.1080/1028415x.1998.11747213] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
Copper plays an important role in cardiac and brain function possibly through endocrine and neuroendocrine systems. The syndrome of copper deficiency is worsened by dietary fructose and other trace metals such as zinc. We investigated the effect of a low copper diet on plasma opioid peptides in 11 healthy young volunteers who were fed foods low in copper but adequate in all other nutrients. The study was divided into three dietary periods. Copper was added to the diet so that the diet contained 0.66 mg/day for 24 days (marginal Cu), 0.38 mg/day for 42 days (low Cu) and 2.49 mg/day for 24 days (adequate Cu). The indices of copper status, ceruloplasmin and plasma copper concentrations, declined and were significantly lower (p < 0.05) at the end of the low Cu period than at the beginning of the study and the end of the marginal Cu period. They increased significantly at the end of the adequate Cu diet to the levels of the marginal Cu diet. Plasma β-endorphin (BEN), Leu-enkephalin (LE), Met-enkephalin (ME) and Adrenocorticotropic hormone (ACTH) were measured by radioimmunoassay at the beginning of the study and at the end of each dietary period. No significant differences were observed in BEN, LE or ME during any of the periods. There were only small increases in LE and ME at the end of marginal and low copper diet periods and no significant changes were observed on copper repletion. Plasma ACTH was significantly lower at the end of low copper compared to baseline value but was not lower after marginal copper. Copper repletion had no significant effect on ACTH. The data show that plasma opioid peptides did not respond significantly to differential copper intake.
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Affiliation(s)
- S J Bhathena
- a USDA, ARS , Beltsville Human Nutrition Research Center, Phytonutrients Laboratory , Beltsville, MD 20705 , USA
| | - M J Werman
- b Department of Food Engineering and Biotechnology , Technion-Israel Institute of Technology , Haifa 32000 , Israel
| | - J R Turnlund
- c Western Human Nutrition Research Center, Agricultural Research Service , San Francisco , CA 94129 , USA
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23
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Bennett DR, Baird CJ, Chan KM, Crookes PF, Bremner CG, Gottlieb MM, Naritoku WY. Zinc toxicity following massive coin ingestion. Am J Forensic Med Pathol 1997; 18:148-53. [PMID: 9185931 DOI: 10.1097/00000433-199706000-00008] [Citation(s) in RCA: 68] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
This is the first reported case of human fatality associated with zinc intoxication following a massive ingestion of coins. Four hundred and sixty-one coins were removed form the gastrointestinal tract of a schizophrenic patient during the course of hospitalization. Many of the post-1981 pennies, which consist primarily of zinc, showed severe corrosion due to their prolonged contact with acidic gastric juice. The patient presented with clinical manifestations consistent with the local corrosive as well as systemic effects of zinc intoxication and died 40 days after admission with multi-system organ failure. Tissue samples of the kidneys, pancreas, and liver obtained at autopsy revealed acute tubular necrosis, mild fibrosis, and acute massive necrosis, respectively, and contained high levels of zinc. The overall effects of zinc intoxication on the various organ systems, possible hematological derangement, and the impairment of copper absorption as well as the outcome with treatment are discussed.
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Affiliation(s)
- D R Bennett
- Department of Pathology, Los Angeles County-University of Southern California Medical Center 90033, USA
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24
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25
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Reeves PG, Rossow KL. Zinc-and/or cadmium-induced intestinal metallothionein and copper metabolism in adult rats. J Nutr Biochem 1996. [DOI: 10.1016/0955-2863(95)00179-4] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
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26
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Hoyt J, Potter G, Greene L, Anderson J. Copper balance in Miniature Horses fed varying amounts of zinc. J Equine Vet Sci 1995. [DOI: 10.1016/s0737-0806(07)80547-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022]
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27
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Reeves PG. Adaptation responses in rats to long-term feeding of high-zinc diets: emphasis on intestinal metallothionein. J Nutr Biochem 1995. [DOI: 10.1016/0955-2863(94)00008-a] [Citation(s) in RCA: 22] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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28
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Yu S, Beynen AC. High zinc intake reduces biliary copper excretion in rats. J Anim Physiol Anim Nutr (Berl) 1994. [DOI: 10.1111/j.1439-0396.1994.tb00385.x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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29
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Zinc-induced metallothionein and copper metabolism in intestinal mucosa, liver, and kidney of rats. Nutr Res 1994. [DOI: 10.1016/s0271-5317(05)80490-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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30
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Reeves PG, Rossow KL, Bobilya DJ. Zinc-induced metallothionein and copper metabolism in intestinal mucosa, liver, and kidney of rats. Nutr Res 1993. [DOI: 10.1016/s0271-5317(05)80791-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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31
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Larsen T, Sandström B. Effect of calcium, copper, and zinc levels in a rapeseed meal diet on mineral and trace element utilization in the rat. Biol Trace Elem Res 1992; 35:167-84. [PMID: 1280982 DOI: 10.1007/bf02783728] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Mineral and trace element interactions were studied in a balance trial with rats. Calcium, copper, and zinc were supplied to a rapeseed meal diet in a factorial design. Animals were fed ad libitum, and absorption, excretion, and retention of the elements were evaluated either as fractions of total intake or in relation to nitrogen retention to account for differences in food intake and lean body mass increment. The intrinsic content of minerals and trace elements was sufficient to support growth at a rate that could be expected from the rapeseed protein quality. However, when calcium was included in the diet, the intrinsic dietary level of zinc appeared to be limiting, despite the fact that the zinc level was twice the recommended level. Additional zinc supply reversed growth impairment. This calcium-zinc interaction is believed to be owing to the formation of phytate complexes. Calcium addition influenced the calcium, phosphorus, magnesium, zinc, and iron--but not the copper--balances. The addition of calcium reduced the availability of the intrinsic zinc, whereas no effect was seen in the zinc-fortified groups. The availability of intrinsic copper was in a similar way significantly impaired by addition of dietary zinc, whereas copper-supplied groups were unaffected by zinc addition. Intrinsic iron availability was also dependent upon zinc addition, although in a more ambiguous way. Thus, addition of extrinsic minerals to a diet high in phytate can result in significant impairments of growth and mineral utilization.
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Affiliation(s)
- T Larsen
- National Institute of Animal Science, Animal Physiology and Biochemistry, Foulum, Tjele, Denmark
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32
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Cao GH, Chen JD. Effects of dietary zinc on free radical generation, lipid peroxidation, and superoxide dismutase in trained mice. Arch Biochem Biophys 1991; 291:147-53. [PMID: 1656886 DOI: 10.1016/0003-9861(91)90117-2] [Citation(s) in RCA: 43] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
The purpose of this study was to investigate the effects of dietary zinc on free radical generation, lipid peroxidation, and superoxide dismutase (SOD) in exercised mice. In the first part of the study, 48 male weanling mice were randomly divided into three groups. They were fed a zinc-deficient diet containing 1.6 mg/kg zinc or were pair-fed or fed ad libitum a zinc-adequate diet supplemented with 50 mg/kg zinc. Half of each group received an exercise training program that consisted of swimming for 60 min per day in deionized water. The diets and exercise program persisted for 6 weeks. In the second part of the study, 64 mice were fed zinc-deficient diets for 6 weeks, and then one group was fed the zinc-deficient diet for an additional 3 weeks, and the other three groups were fed diets supplemented with 5, 50, and 500 mg/kg zinc, respectively. Half of each group also received the exercise program. Both blood and liver samples were examined. Free radicals in liver were directly detected by electron spin resonance techniques and the extent of lipid peroxidation was indicated by malonic dialdehyde (MDA). Both CuZn-SOD and Mn-SOD were measured. The results showed that exercise training increased the metabolism of zinc, and zinc deficiency induced an increased free radical generation and lipid peroxidation and a decreased hepatic CuZn-SOD activity in exercised mice. Furthermore, although exercise training had no effect on the level of free radicals in zinc-adequate mice, it could increase the hepatic mitochondrial MDA formation further in zinc-deficient animals and zinc deficiency would eliminate the exercise-induced increase in SOD activities which existed in zinc-adequate mice. A total of 50 mg/kg zinc supplemented in the diet was adequate to correct the zinc-deficient status in exercised mice while 5 mg/kg zinc had a satisfactory effect on the recovery of only sedentary zinc-deficient mice. However, 500 mg/kg zinc had a harmful effect on both sedentary and exercised zinc-deficient animals.
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Affiliation(s)
- G H Cao
- Research Division of Nutrition and Biochemistry, Beijing Medical University, People's Republic of China
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33
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Aulerich RJ, Bursian SJ, Poppenga RH, Braselton WE, Mullaney TP. Toleration of high concentrations of dietary zinc by mink. J Vet Diagn Invest 1991; 3:232-7. [PMID: 1911995 DOI: 10.1177/104063879100300309] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
Adult and kit male and female natural dark ranch mink (Mustela vison) were fed a conventional diet supplemented with 0, 500, 1,000, or 1,500 ppm zinc, as ZnSO4.7H2O, for 144 days. No marked adverse effects were observed in feed consumption, body weight gains, hematologic parameters, fur quality, or survival. Zinc concentrations in liver, kidney, and pancreas of the mink increased in direct proportion to the zinc content of the diet. Histopathologic examination of the livers, kidneys, and pancreata revealed no lesions indicative of zinc toxicosis. The results indicate that mink can tolerate at least 1,500 ppm dietary zinc, as ZnSO4.7H2O, for several months without apparent adverse effects.
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Affiliation(s)
- R J Aulerich
- Department of Animal Science, Michigan State University, East Lansing 48824
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34
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Abdel-Mageed AB, Oehme FW. The effect of various dietary zinc concentrations on the biological interactions of zinc, copper, and iron in rats. Biol Trace Elem Res 1991; 29:239-56. [PMID: 1726407 DOI: 10.1007/bf03032681] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
Three groups (14 rats each) were fed one of the following diets for 8 wks: a control purified basal diet containing 12 ppm zinc, 5 ppm copper, and 35 ppm iron; the basal diet with less than 2 ppm zinc; or the basal diet supplemented with 1000 ppm zinc. Rats fed the zinc-deficient diet had decreased weight gain, moderate polydipsia, and intermittent mild diarrhea. The zinc-supplemented rats had a cyclical pattern of food intake and weight loss from weeks 5 to 8. Tissue concentrations suggest that zinc and copper were not mutually antagonistic with chronic dietary imbalances. If tissue element concentrations reflected intestinal uptake, then competition and/or inhibition of intestinal uptake occurred between zinc and iron. The fluctuations in tissue element concentrations that occurred with increased duration of the study were at variance with previous studies of shorter time periods. The dietary proportions of zinc, copper, and iron appear to influence zinc, copper, and iron metabolism at the intestinal and cellular transport levels over a given period of time.
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Affiliation(s)
- A B Abdel-Mageed
- Comparative Toxicology Laboratories, Kansas State University, Manhattan 66506-5606
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35
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36
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Miller WJ, Amos HE, Gentry RP, Blackmon DM, Durrance RM, Crowe CT, Fielding AS, Neathery MW. Long-term feeding of high zinc sulfate diets to lactating and gestating dairy cows. J Dairy Sci 1989; 72:1499-508. [PMID: 2760310 DOI: 10.3168/jds.s0022-0302(89)79260-2] [Citation(s) in RCA: 20] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
Thirty dairy cows, fed a control diet consisting of silage and concentrates, were given either 0, 1000, or 2000 ppm of supplemental Zn (DM basis), from zinc sulfate monohydrate (ZnSO4.H2O) for most of a lactation. Feeding 2000 ppm Zn decreased milk yield and feed intake after several weeks. Some cows were affected more severely than others. Generally, primiparous animals were more tolerant of the high Zn diet than multiparous cows. Milk Zn was materially higher for cows fed 1000 ppm added Zn than controls. With 2000 ppm Zn, milk Zn was elevated further but returned to control values when the high Zn diet was discontinued. Plasma Zn was higher in cows fed supplemental Zn with the increase from 1000 to 2000 greater than that for the first addition. Plasma Cu was lower in cows feed 2000 ppm Zn but milk Cu was not reduced. Milk fat content was not affected, but protein and SNF were reduced by the 12th wk with the 2000 ppm Zn diet. There was no apparent effect on long-term health or performance after the cows were removed from the 2000 ppm Zn diet. Except for lower calf weights with 2000 ppm Zn, reproductive performance was not measurably affected by the dietary treatments. The 1000 ppm added Zn diet had no adverse effect on the cows in any parameter measured.
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Affiliation(s)
- W J Miller
- Department of Animal and Dairy Science, University of Georgia, Athens 30602
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37
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Stahl JL, Greger JL, Cook ME. Zinc, copper and iron utilisation by chicks fed various concentrations of zinc. Br Poult Sci 1989; 30:123-34. [PMID: 2743167 DOI: 10.1080/00071668908417131] [Citation(s) in RCA: 29] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
1. Zinc, iron and copper interactions were examined in chicks (New Hampshire X Single Comb White Leghorn) grown individually in stainless steel cages and fed on purified diets with three concentrations of zinc: control (37 mg Zn/kg), moderate (100 mg Zn/kg) and excess (2000 mg Zn/kg) in three studies. 2. Chicks given either moderate or excess zinc excreted more than twice as much 65Zn from a test diet as those fed on the control diet. Thus chicks given the moderate amount of zinc had concentrations of zinc in tissues similar to those of controls but chicks given excess zinc accumulated zinc in their tissues. 3. The specific activity of 65Zn in the tissues, especially in the bursa of Fabricius, of chicks given excess zinc was not reduced as much as would be predicted. Thus, ingestion of excess zinc appeared to reduce tissue turnover of 65Zn, especially in the bursa. However, humoral immune responses, as measured by antibody titres to sheep red blood cells, were not affected. 4. Chicks given excess zinc or pair-fed on the control diet retained less 59Fe from a test diet than chicks given control or moderate concentrations of zinc ad libitum. The iron concentrations in tibiae of chicks given excess zinc were depressed.
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Affiliation(s)
- J L Stahl
- Department of Nutritional Sciences, University of Wisconsin, Madison 53706
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38
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Parsons CM, Baker DH, Welch CC. Effect of excess zinc on iron utilization by chicks fed a diet devoid of phytate and fiber. Nutr Res 1989. [DOI: 10.1016/s0271-5317(89)80009-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
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Stevenson MH, Gibson SW, Jackson N. Withdrawal of zinc oxide-containing diets from mature, female domestic fowl: effects on selected tissue mineral contents. Br Poult Sci 1987; 28:449-59. [PMID: 3676878 DOI: 10.1080/00071668708416979] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
1. Two hundred and sixteen laying hens of two strains were given diets containing ZnO to provide 0, 0.5, 0.75, 1.00, 1.25, 1.50, 2.00, 3.00 or 4.00 g added Zn/kg. These diets were offered ad libitum for 5 consecutive 28-d periods. All hens were subsequently offered the control diet with no added ZnO for 5 weeks. 2. Four hens from each treatment were killed 0, 1 and 5 weeks after substitution of the ZnO-supplemented diets by the control diet. 3. Dietary addition of ZnO significantly increased liver, kidneys, pancreas and gizzard Zn contents but this effect was rapidly reversed on removal of the ZnO-containing diets. 4. Hepatic and renal Fe contents were significantly depressed by dietary ZnO but after substitution of these diets by the control diet the values were comparable to that of the controls. 5. Liver Cu content declined significantly as dietary ZnO concentration increased but there was a return towards normal after ZnO withdrawal. Renal, pancreatic and gizzard Cu contents showed quadratic responses to added ZnO. 6. After ZnO withdrawal for 5 weeks, pancreas Cu contents declined linearly, whereas renal and gizzard Cu values were similar for all treatments. 7. Overall the long-term feeding of ZnO-supplemented diets followed by a period of withdrawal of the ZnO supplement had no detrimental effects on tissue mineral contents.
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Affiliation(s)
- M H Stevenson
- Agricultural and Food Chemistry Research Division, Department of Agriculture for Northern Ireland, Belfast
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Abstract
Zinc is a common element in the human environment and constitutes an important trace element intervening in many biological processes. Toxicity of zinc is low; zinc deficiency represents, however, a hazard for human health. Zinc is not mutagenic and has little, if any, clastogenic properties. Zinc can induce tumours but only following local application, and does not represent a carcinogenic risk to man. It is still uncertain whether zinc can cause malignant transformation but zinc is needed for cellular proliferation of existing tumours and tumour growth is retarded by zinc deficiency. Zinc is not teratogenic; it can, in fact, avert teratogenicity of other agents. Conversely, zinc deficiency may be harmful to the developing organism.
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41
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Gibson SW, Stevenson MH, Jackson N. Comparison of the effects of feeding diets supplemented with zinc oxide or zinc acetate on the performance and tissue mineral content of mature female fowls. Br Poult Sci 1986; 27:391-402. [PMID: 3791016 DOI: 10.1080/00071668608416895] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
An experiment is reported in which zinc, as acetate or oxide, was fed to laying hens for 10 weeks at concentrations equivalent to 1, 2, 3, 4 and 5 g added Zn/kg diet. Both concentration and form of Zn additive significantly reduced food, water and Zn intakes, egg production and body weight, the acetate having a greater detrimental effect than the oxide at equivalent added Zn inclusion. Zinc acetate depressed the fresh weight/kg body weight of the kidneys, ovary and oviduct to a greater extent than the corresponding oxide treatments. Concentration, but not form of additive, significantly reduced liver and pancreas weights and liver lipid concentration, while spleen and gizzard weights showed increases. Overall, the additives significantly increased the Zn and Fe concentrations of the liver, kidneys, pancreas and gizzard. Zinc concentrations of liver, pancreas and gizzard and Fe concentrations of liver were consistently higher for the acetate-fed birds. Liver, pancreas and gizzard Cu concentrations significantly declined as inclusion rate of Zn increased.
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Jackson N, Gibson SW, Stevenson MH. Effects of short- and long-term feeding of zinc oxide-supplemented diets on the mature, female domestic fowl with special reference to tissue mineral content. Br J Nutr 1986; 55:333-49. [PMID: 3676162 DOI: 10.1079/bjn19860040] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
1. In Expt 1, the effects on laying hens of diets supplemented with zinc oxide providing up to 20 g added zinc/kg were compared. In Expt 2 the diets contained up to 6 g added Zn/kg. 2. In both experiments, food intake, body-weight, egg number, and liver, oviduct and ovary weights/kg body-weight were significantly reduced by added ZnO; gizzard weight/kg body-weight was significantly increased. In Expt 2, pancreas weight was significantly reduced by added ZnO. 3. Liver, kidney and pancreatic Zn and iron concentrations were significantly elevated in both experiments. 4. In both experiments, liver, kidneys and pancreatic copper concentrations gave quadratic responses to added ZnO.
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Affiliation(s)
- N Jackson
- Agricultural and Food Chemistry Research Division, Department of Agriculture for Northern Ireland, Belfast
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43
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Gromadzka-Ostrowska J, Zalewska B, Jakubów K, Gozlinski H. Three-year study on trace mineral concentration in the blood plasma of Shetland pony mares. COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY. A, COMPARATIVE PHYSIOLOGY 1985; 82:651-60. [PMID: 2866888 DOI: 10.1016/0300-9629(85)90447-5] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
Changes in some trace minerals concentrations (calcium, inorganic phosphorus, magnesium, zinc, iron, copper, sodium and potassium) in blood plasma were investigated during a three-year period in Shetland pony mares. Blood plasma mineral concentrations were determined by the atomic absorption method and colorimetric method. The three-year averages were in micrograms/ml; Na 4630 +/- 168; K 277 +/- 3.8; Ca 171 +/- 3.8; P 31.5 +/- 0.74; Fe 1.92 +/- 0.14; Zn 1.07 +/- 0.04 and Cu 1.06 +/- 0.02. Two trace minerals (magnesium in inorganic phosphorus) showed only long-term tendency changes--upward or downward trends were not connected with the season. Most of the investigated minerals showed both a long-term change tendency and more or less marked seasonally related concentration changes, being higher during autumn or winter (zinc, sodium), or during spring and summer (calcium, copper, iron and potassium). Some interrelationships between particular trace mineral concentrations in blood plasma were also observed.
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44
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Zinc supplementation of optimal and suboptimal protein diets 2. Responses of young rats fed protein combinations. Nutr Res 1985. [DOI: 10.1016/s0271-5317(85)80024-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Tocco-Bradley R, Kluger MJ. Zinc concentration and survival in rats infected with Salmonella typhimurium. Infect Immun 1984; 45:332-8. [PMID: 6746092 PMCID: PMC263225 DOI: 10.1128/iai.45.2.332-338.1984] [Citation(s) in RCA: 24] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open
Abstract
Percent survival was measured in male rats injected intravenously with live Salmonella typhimurium when plasma and tissue zinc levels were manipulated. Alzet pumps implanted intraperitoneally infused zinc gluconate or sodium gluconate (controls) from the onset of infection to 72 h postinfection. Plasma and tissue zinc levels were manipulated by infusing (i) 180 micrograms of Zn per h to achieve supranormal plasma and tissue zinc concentrations, (ii) 120 micrograms of Zn per h to prevent the infection-induced fall and to maintain plasma zinc levels at noninfection levels while raising tissue levels above that of infected controls, and (iii) 30 micrograms of Zn per h to increase tissue zinc levels while allowing the infection-induced decrease in plasma zinc. Preventing the fall in plasma zinc while raising liver zinc to supranormal levels enhanced rather than reduced percent survival; raising plasma and liver zinc to supranormal levels returned survival to control levels. Loading the liver with an excess of zinc without changing plasma zinc (30 micrograms of Zn per h) did not increase percent survival in the infected host. Pretreatment or administration of zinc at the time of infection led to increased percent survival compared with administration of zinc 4 h after the onset of infection.
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Dewar WA, Wight PA, Pearson RA, Gentle MJ. Toxic effects of high concentrations of zinc oxide in the diet of the chick and laying hen. Br Poult Sci 1983; 24:397-404. [PMID: 6616303 DOI: 10.1080/00071668308416754] [Citation(s) in RCA: 38] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
The effects of high dietary concentrations of zinc oxide on chicks and hens were studied in four experiments. Chicks given 2000, 4000 or 6000 mg zinc/kg diet from 2 to 6 weeks of age grew poorly, many showing gizzard erosion and lesions of the exocrine pancreas. Dissecting aneurysms occurred in a few birds receiving 6000 mg zinc/kg. Pancreatic lesions were found in chicks maintained on 1000, 2000 or 4000 mg zinc/kg from 0 to 4 weeks and the two higher concentrations reduced body weight and increased the incidence of gizzard erosion. Histologically, gizzard lesions varied from excessive desquamation of epithelial cells, heterophils and erythrocytes into an abnormally spongiform koilin, to erosion of koilin, glands and pits. Pancreatic lesions could be detected only microscopically and consisted of dilation of the acinar lumina, cytoplasmic vacuolation, cytoplasmic globule formation and necrosis of the exocrine cells with interparenchymal fibrosis. Similar lesions of the gizzard and pancreas were found in hens after they had received 10000 or 20000 mg zinc/kg diet for only 4 d. Hens given 10000 mg zinc/kg for 4 d followed by a normal zinc intake for 28 d had normal gizzards and pancreata.
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ZEMEL MICHAELB, BIDARI MOLOOKT. Zinc, Iron and Copper Availability as Affected by Orthophosphates, Polyphosphates and Calcium. J Food Sci 1983. [DOI: 10.1111/j.1365-2621.1983.tb10791.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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48
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Fitzsimons RB, Soltan MH. Congenital skin defects and zinc deficiency - a possible relationship. Eur J Obstet Gynecol Reprod Biol 1981; 12:79-84. [PMID: 7198590 DOI: 10.1016/0028-2243(81)90019-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
Two infants with congenital skin defects were born to mothers who had uneventful pregnancies; drugs were not ingested, nor was any infection noted. Maternal plasma zinc and copper were measured postnatally and were found to be abnormal. We suggest that these skin abnormalities were related to maternal zinc deficiency.
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Hamilton R, Fox M, Tao SH, Fry B. Zinc-induced anemia in young japanese quail ameliorated by supplemental copper and iron. Nutr Res 1981. [DOI: 10.1016/s0271-5317(81)80089-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
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50
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Petering HG. The influence of dietary zinc and copper on the biologic effects of orally ingested lead in the rat. Ann N Y Acad Sci 1980; 355:298-308. [PMID: 6940484 DOI: 10.1111/j.1749-6632.1980.tb21348.x] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
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