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Fang H, Sissener NH, Sæle Ø, Sigholt T, Philip AJP. The Interaction Between Dietary Fat Level, n-3 LC-PUFA, and Zinc on Their Postprandial Absorption Kinetics in Atlantic Salmon ( Salmo salar). AQUACULTURE NUTRITION 2024; 2024:6173690. [PMID: 39759461 PMCID: PMC11699991 DOI: 10.1155/anu/6173690] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/28/2024] [Accepted: 11/11/2024] [Indexed: 01/07/2025]
Abstract
Two short-term feeding trials were conducted on Salmo salar, with the interaction between dietary zinc (Zn) and fat level in trial 1 and with the interaction between dietary Zn and n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) in trial 2, focusing on postprandial plasma parameters, intestinal Zn and fat uptake and transport. After 4-week feeding interventions, samples were collected at different postprandial time points, ranging from 0 to 36/38 h after feeding. Results showed that increased Zn level in feed significantly increased the postprandial plasma Zn level in trial 1 (8-9°C). On the contrary, the postprandial plasma Zn level was not affected by the dietary Zn under higher temperature conditions (trial 2, 10-12°C). Further, analyzed markers related to intestinal Zn uptake and transport were not affected by dietary fat level and n-3 LC-PUFA. In addition, analyzed markers related to intestinal fat uptake and transport were not affected by dietary Zn. Intestinal Zn transport plays a key role in regulating body Zn storage, while intestinal fat transport influences lipid accumulation within the intestine. Understanding how these processes respond to dietary components is critical for maintaining fish health and welfare.
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Affiliation(s)
- HaoHang Fang
- Feed and Nutrition, Institute of Marine Research, Bergen, Norway
- Department of Biological Sciences (BIO), University of Bergen, Bergen, Norway
| | - Nini H Sissener
- Feed and Nutrition, Institute of Marine Research, Bergen, Norway
| | - Øystein Sæle
- Feed and Nutrition, Institute of Marine Research, Bergen, Norway
| | | | - Antony J Prabhu Philip
- Norwegian Institute of Food, Fisheries and Aquaculture Research (Nofima), Bergen, Norway
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2
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Feng Y, Liu Y, Liu W, Ding X, James Kang Y. Zinc-glutathione mitigates alcohol-induced intestinal and hepatic injury by modulating intestinal zinc-transporters in mice. J Nutr Biochem 2024; 132:109697. [PMID: 38964724 DOI: 10.1016/j.jnutbio.2024.109697] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2024] [Revised: 06/24/2024] [Accepted: 06/27/2024] [Indexed: 07/06/2024]
Abstract
Long-term alcohol overconsumption impairs intestinal and hepatic structure and function, along with dysregulation of zinc homeostasis. We previously found that zinc-glutathione (Zn-GSH) complex effectively suppressed alcohol-induced liver injury in mice. This study was undertaken to test the hypothesis that Zn-GSH suppresses alcohol-induced liver injury by modulating intestinal zinc transporters. Mice were subjected to long-term ethanol feeding, as per the NIAAA model, with groups receiving either an ethanol diet alone or an ethanol diet supplemented with Zn-GSH. Treatment groups were carefully monitored for alcohol consumption and subjected to a final binge drinking exposure. The results showed that Zn-GSH increased the survival rate and decreased the recovery time from binge drinking-induced drunkenness. Histopathological analyses demonstrated a reduction in liver steatosis and the preservation of intestinal integrity by Zn-GSH. It was observed that Zn-GSH prevented the reduction of Zn and GSH levels while increasing alcohol dehydrogenase and aldehyde dehydrogenase in both liver and intestine. Importantly, the expression and protein abundance of zinc transporters ZnT-1, ZIP-1, ZIP-4, ZIP-6, and ZIP-14, all of which are critically involved in intestinal zinc transport and homeostasis, were significantly increased or preserved by Zn-GSH in response to alcohol exposure. This study thus highlights the critical role of Zn-GSH in maintaining intestinal zinc homeostasis by modulating zinc transporters, thereby preventing alcohol-induced intestinal and hepatic injury.
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Affiliation(s)
- Yinrui Feng
- Regenerative Medicine Research Center, Sichuan University West China Hospital, Chengdu, Sichuan, China
| | - Yundi Liu
- Regenerative Medicine Research Center, Sichuan University West China Hospital, Chengdu, Sichuan, China
| | - Wenrui Liu
- Regenerative Medicine Research Center, Sichuan University West China Hospital, Chengdu, Sichuan, China
| | - Xueqin Ding
- Regenerative Medicine Research Center, Sichuan University West China Hospital, Chengdu, Sichuan, China
| | - Y James Kang
- Regenerative Medicine Research Center, Sichuan University West China Hospital, Chengdu, Sichuan, China.
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3
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Borkowska-Sztachańska M, Thoene M, Socha K, Juśkiewicz J, Majewski MS. Decreased vascular contraction and changes in oxidative state in middle-aged Wistar rats after exposure to increased levels of dietary zinc. Toxicol Appl Pharmacol 2024; 491:117049. [PMID: 39098745 DOI: 10.1016/j.taap.2024.117049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2024] [Revised: 07/14/2024] [Accepted: 08/01/2024] [Indexed: 08/06/2024]
Abstract
Both copper and zinc are known to be important for maintaining health, but most research has focused on deficiencies of these elements. Recent studies have shown that high levels of Cu can be toxic, especially to the cardiovascular (CV) system. However, little research has been done on the effects of higher levels of Zn on the CV system. In this study, male Wistar rats aged 12 months were given a diet with twice the recommended daily allowance of zinc (31.8 mg/kg of diet) and compared to a control group (15.9 mg/kg of diet) after 8 weeks. Blood plasma and internal organs of both groups were examined for levels of copper, zinc, selenium and iron, as well as several key enzymes. Aortic rings from both groups were also examined to determine vascular functioning. There were very few changes in the vascular system functioning after chronic exposure to zinc, and only one enzyme, heme oxygenase-1 (HO-1) was elevated, whereas vascular contraction to noradrenaline decreased with no changes in vasodilation to acetylcholine. Of the micronutrients, zinc and selenium were elevated in the blood plasma, while copper decreased. Meanwhile, the total antioxidant status increased. These were not observed in the liver. Therefore, it is proposed that there is a mechanism in place within the vascular system to protect against the overproduction of heme, caused by chronic zinc exposure.
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Affiliation(s)
- Małgorzata Borkowska-Sztachańska
- Department of Mental and Psychosomatic Diseases, Faculty of Medicine, University of Warmia and Mazury in Olsztyn, 10-082 Olsztyn, Poland.
| | - Michael Thoene
- Department of Medical Biology, Faculty of Health Sciences, University of Warmia and Mazury in Olsztyn, 10-561 Olsztyn, Poland.
| | - Katarzyna Socha
- Department of Bromatology, Medical University of Białystok, 15-222 Białystok, Poland.
| | - Jerzy Juśkiewicz
- Division of Food Science, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-748 Olsztyn, Poland.
| | - Michał S Majewski
- Department of Pharmacology and Toxicology, Faculty of Medicine, University of Warmia and Mazury in Olsztyn, 10-082 Olsztyn, Poland.
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4
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Gale J, Aizenman E. The physiological and pathophysiological roles of copper in the nervous system. Eur J Neurosci 2024; 60:3505-3543. [PMID: 38747014 PMCID: PMC11491124 DOI: 10.1111/ejn.16370] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2023] [Revised: 02/28/2024] [Accepted: 04/10/2024] [Indexed: 07/06/2024]
Abstract
Copper is a critical trace element in biological systems due the vast number of essential enzymes that require the metal as a cofactor, including cytochrome c oxidase, superoxide dismutase and dopamine-β-hydroxylase. Due its key role in oxidative metabolism, antioxidant defence and neurotransmitter synthesis, copper is particularly important for neuronal development and proper neuronal function. Moreover, increasing evidence suggests that copper also serves important functions in synaptic and network activity, the regulation of circadian rhythms, and arousal. However, it is important to note that because of copper's ability to redox cycle and generate reactive species, cellular levels of the metal must be tightly regulated to meet cellular needs while avoiding copper-induced oxidative stress. Therefore, it is essential that the intricate system of copper transporters, exporters, copper chaperones and copper trafficking proteins function properly and in coordinate fashion. Indeed, disorders of copper metabolism such as Menkes disease and Wilson disease, as well as diseases linked to dysfunction of copper-requiring enzymes, such as SOD1-linked amyotrophic lateral sclerosis, demonstrate the dramatic neurological consequences of altered copper homeostasis. In this review, we explore the physiological importance of copper in the nervous system as well as pathologies related to improper copper handling.
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Affiliation(s)
- Jenna Gale
- Department of Neurobiology and Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Elias Aizenman
- Department of Neurobiology and Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
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5
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Jin D, Wei X, He Y, Zhong L, Lu H, Lan J, Wei Y, Liu Z, Liu H. The nutritional roles of zinc for immune system and COVID-19 patients. Front Nutr 2024; 11:1385591. [PMID: 38706559 PMCID: PMC11066294 DOI: 10.3389/fnut.2024.1385591] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2024] [Accepted: 04/09/2024] [Indexed: 05/07/2024] Open
Abstract
Zinc (Zn) is a vital micronutrient that strengthens the immune system, aids cellular activities, and treats infectious diseases. A deficiency in Zn can lead to an imbalance in the immune system. This imbalance is particularly evident in severe deficiency cases, where there is a high susceptibility to various viral infections, including COVID-19 caused by SARS-CoV-2. This review article examines the nutritional roles of Zn in human health, the maintenance of Zn concentration, and Zn uptake. As Zn is an essential trace element that plays a critical role in the immune system and is necessary for immune cell function and cell signaling, the roles of Zn in the human immune system, immune cells, interleukins, and its role in SARS-CoV-2 infection are further discussed. In summary, this review paper encapsulates the nutritional role of Zn in the human immune system, with the hope of providing specific insights into Zn research.
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Affiliation(s)
- Di Jin
- Guangxi Key Laboratory of Metabolic Reprogramming and Intelligent Medical Engineering for Chronic Diseases, Department of Laboratory Medicine, Guangxi Clinical Research Center for Diabetes and Metabolic Diseases, The Second Affiliated Hospital of Guilin Medical University, Guilin, China
- College of Medical Laboratory Science, Guilin Medical University, Guilin, China
| | - Xinran Wei
- Guangxi Key Laboratory of Metabolic Reprogramming and Intelligent Medical Engineering for Chronic Diseases, Department of Laboratory Medicine, Guangxi Clinical Research Center for Diabetes and Metabolic Diseases, The Second Affiliated Hospital of Guilin Medical University, Guilin, China
- College of Medical Laboratory Science, Guilin Medical University, Guilin, China
| | - Yunyi He
- College of Medical Laboratory Science, Guilin Medical University, Guilin, China
| | - Luying Zhong
- College of Medical Laboratory Science, Guilin Medical University, Guilin, China
| | - Huijie Lu
- College of Medical Laboratory Science, Guilin Medical University, Guilin, China
| | - Jiaxin Lan
- College of Medical Laboratory Science, Guilin Medical University, Guilin, China
| | - Yuting Wei
- College of Medical Laboratory Science, Guilin Medical University, Guilin, China
| | - Zheng Liu
- College of Medical Laboratory Science, Guilin Medical University, Guilin, China
| | - Hongbo Liu
- Guangxi Key Laboratory of Metabolic Reprogramming and Intelligent Medical Engineering for Chronic Diseases, Department of Laboratory Medicine, Guangxi Clinical Research Center for Diabetes and Metabolic Diseases, The Second Affiliated Hospital of Guilin Medical University, Guilin, China
- College of Medical Laboratory Science, Guilin Medical University, Guilin, China
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6
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Mikulska J, Pietrzak D, Rękawek P, Siudaj K, Walczak-Nowicka ŁJ, Herbet M. Celiac disease and depressive disorders as nutritional implications related to common factors - A comprehensive review. Behav Brain Res 2024; 462:114886. [PMID: 38309373 DOI: 10.1016/j.bbr.2024.114886] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Revised: 01/23/2024] [Accepted: 01/27/2024] [Indexed: 02/05/2024]
Abstract
Celiac disease (CD) is an immune-mediated disease affecting the small intestine. The only treatment strategy for CD is the gluten-free diet (GFD). One of the more common mental disorders in CD patients is major depressive disorder (MDD). The influence of GFD on the occurrence of MDD symptoms in patients with CD will be evaluated. This diet often reduces nutritional deficiencies in these patients and also helps to reduce depressive symptoms. Both disease entities are often dominated by the same deficiencies of nutrients such as iron, zinc, selenium, iodine, or B and D vitamins. Deficiencies of particular components in CD can favor MDD and vice versa. Gluten can adversely affect the mental state of patients without CD. Also, intestinal microbiota may play an important role in the described process. This work aims to comprehensively assess the common factors involved in the pathomechanisms of MDD and CD, with particular emphasis on nutrient imbalances. Given the complexity of both disease entities, and the many common links, more research related to improving mental health in these patients and the implementation of a GFD would need to be conducted, but it appears to be a viable pathway to improving the quality of life and health of people struggling with CD and MDD. Therefore, probiotics, micronutrients, macronutrients, and vitamin supplements are recommended to reduce the risk of MDD, given that they may alleviate the symptoms of both these disease entities. In turn, in patients with MDD, it is worth considering testing for CD.
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Affiliation(s)
- Joanna Mikulska
- Chair and Department of Toxicology, Faculty of Pharmacy, Medical University of Lublin, 8 Chodźki Street, 20-093 Lublin, Poland
| | - Diana Pietrzak
- Chair and Department of Toxicology, Faculty of Pharmacy, Medical University of Lublin, 8 Chodźki Street, 20-093 Lublin, Poland
| | - Paweł Rękawek
- Chair and Department of Toxicology, Faculty of Pharmacy, Medical University of Lublin, 8 Chodźki Street, 20-093 Lublin, Poland
| | - Krystian Siudaj
- Chair and Department of Toxicology, Faculty of Pharmacy, Medical University of Lublin, 8 Chodźki Street, 20-093 Lublin, Poland
| | - Łucja Justyna Walczak-Nowicka
- Chair and Department of Toxicology, Faculty of Pharmacy, Medical University of Lublin, 8 Chodźki Street, 20-093 Lublin, Poland.
| | - Mariola Herbet
- Chair and Department of Toxicology, Faculty of Pharmacy, Medical University of Lublin, 8 Chodźki Street, 20-093 Lublin, Poland
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7
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Stiles LI, Ferrao K, Mehta KJ. Role of zinc in health and disease. Clin Exp Med 2024; 24:38. [PMID: 38367035 PMCID: PMC10874324 DOI: 10.1007/s10238-024-01302-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Accepted: 01/23/2024] [Indexed: 02/19/2024]
Abstract
This review provides a concise overview of the cellular and clinical aspects of the role of zinc, an essential micronutrient, in human physiology and discusses zinc-related pathological states. Zinc cannot be stored in significant amounts, so regular dietary intake is essential. ZIP4 and/or ZnT5B transport dietary zinc ions from the duodenum into the enterocyte, ZnT1 transports zinc ions from the enterocyte into the circulation, and ZnT5B (bidirectional zinc transporter) facilitates endogenous zinc secretion into the intestinal lumen. Putative promoters of zinc absorption that increase its bioavailability include amino acids released from protein digestion and citrate, whereas dietary phytates, casein and calcium can reduce zinc bioavailability. In circulation, 70% of zinc is bound to albumin, and the majority in the body is found in skeletal muscle and bone. Zinc excretion is via faeces (predominantly), urine, sweat, menstrual flow and semen. Excessive zinc intake can inhibit the absorption of copper and iron, leading to copper deficiency and anaemia, respectively. Zinc toxicity can adversely affect the lipid profile and immune system, and its treatment depends on the mode of zinc acquisition. Acquired zinc deficiency usually presents later in life alongside risk factors like malabsorption syndromes, but medications like diuretics and angiotensin-receptor blockers can also cause zinc deficiency. Inherited zinc deficiency condition acrodermatitis enteropathica, which occurs due to mutation in the SLC39A4 gene (encoding ZIP4), presents from birth. Treatment involves zinc supplementation via zinc gluconate, zinc sulphate or zinc chloride. Notably, oral zinc supplementation may decrease the absorption of drugs like ciprofloxacin, doxycycline and risedronate.
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Affiliation(s)
- Lucy I Stiles
- Faculty of Life Sciences and Medicine, GKT School of Medical Education, King's College London, London, UK
| | - Kevin Ferrao
- Faculty of Life Sciences and Medicine, GKT School of Medical Education, King's College London, London, UK
| | - Kosha J Mehta
- Faculty of Life Sciences and Medicine, Centre for Education, King's College London, London, UK.
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Briassoulis G, Briassoulis P, Ilia S, Miliaraki M, Briassouli E. The Anti-Oxidative, Anti-Inflammatory, Anti-Apoptotic, and Anti-Necroptotic Role of Zinc in COVID-19 and Sepsis. Antioxidants (Basel) 2023; 12:1942. [PMID: 38001795 PMCID: PMC10669546 DOI: 10.3390/antiox12111942] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2023] [Revised: 10/26/2023] [Accepted: 10/28/2023] [Indexed: 11/26/2023] Open
Abstract
Zinc is a structural component of proteins, functions as a catalytic co-factor in DNA synthesis and transcription of hundreds of enzymes, and has a regulatory role in protein-DNA interactions of zinc-finger proteins. For many years, zinc has been acknowledged for its anti-oxidative and anti-inflammatory functions. Furthermore, zinc is a potent inhibitor of caspases-3, -7, and -8, modulating the caspase-controlled apoptosis and necroptosis. In recent years, the immunomodulatory role of zinc in sepsis and COVID-19 has been investigated. Both sepsis and COVID-19 are related to various regulated cell death (RCD) pathways, including apoptosis and necroptosis. Lack of zinc may have a negative effect on many immune functions, such as oxidative burst, cytokine production, chemotaxis, degranulation, phagocytosis, and RCD. While plasma zinc concentrations decline swiftly during both sepsis and COVID-19, this reduction is primarily attributed to a redistribution process associated with the inflammatory response. In this response, hepatic metallothionein production increases in reaction to cytokine release, which is linked to inflammation, and this protein effectively captures and stores zinc in the liver. Multiple regulatory mechanisms come into play, influencing the uptake of zinc, the binding of zinc to blood albumin and red blood cells, as well as the buffering and modulation of cytosolic zinc levels. Decreased zinc levels are associated with increasing severity of organ dysfunction, prolonged hospital stay and increased mortality in septic and COVID-19 patients. Results of recent studies focusing on these topics are summarized and discussed in this narrative review. Existing evidence currently does not support pharmacological zinc supplementation in patients with sepsis or COVID-19. Complementation and repletion should follow current guidelines for micronutrients in critically ill patients. Further research investigating the pharmacological mechanism of zinc in programmed cell death caused by invasive infections and its therapeutic potential in sepsis and COVID-19 could be worthwhile.
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Affiliation(s)
- George Briassoulis
- Postgraduate Program “Emergency and Intensive Care in Children, Adolescents, and Young Adults”, School of Medicine, University of Crete, 71003 Heraklion, Greece;
| | - Panagiotis Briassoulis
- Second Department of Anesthesiology, Attikon University Hospital, School of Medicine, National and Kapodistrian University of Athens, 12462 Athens, Greece;
| | - Stavroula Ilia
- Postgraduate Program “Emergency and Intensive Care in Children, Adolescents, and Young Adults”, School of Medicine, University of Crete, 71003 Heraklion, Greece;
- Paediatric Intensive Care Unit, University Hospital, School of Medicine, University of Crete, 71110 Heraklion, Greece;
| | - Marianna Miliaraki
- Paediatric Intensive Care Unit, University Hospital, School of Medicine, University of Crete, 71110 Heraklion, Greece;
| | - Efrossini Briassouli
- Infectious Diseases Department “MAKKA”, First Department of Paediatrics, “Aghia Sophia” Children’s Hospital, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece;
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Li N, Wang R, Deng Z, Zhou J, Li W, Du Q, Zheng L. Structural Characterization of Zinc-Sucrose Complex and Its Ability to Promote Zinc Absorption in Caco-2 Monolayer Cells and Mice. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2023; 71:12094-12104. [PMID: 37493257 DOI: 10.1021/acs.jafc.3c02806] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/27/2023]
Abstract
Sucrose emerges as a metal-ion chelating agent with excellent stability that may increase metal-ion absorption. This study aimed to characterize the structure of zinc-sucrose complex and investigate its ability to promote zinc absorption in Caco-2 monolayer cells and mice. Based on the results of the inductively coupled plasma emission spectrometer (ICP-ES), scanning electron microscopy-energy-dispersive X-ray spectroscopy (SEM-EDX), and Fourier transform infrared spectroscopy (FT-IR), it can be inferred that zinc and sucrose were chelated at a 1:1 ratio, with the hydroxyl groups playing a significant role. The Caco-2 monolayer cell model revealed that zinc-sucrose complex increased the amount of zinc uptake, retention, and transport in a dose- and time-dependent manner. Through the upregulation of genes and proteins for ZIP4, MT1, and DMT1, treatment with zinc-sucrose complex improved the proportion of absorbed zinc utilized for transport compared to ZnCl2 (26.21 ± 4.96 versus 8.50 ± 1.51%). Pharmacokinetic analysis of mice confirmed the zinc absorption-promoting effect of zinc-sucrose complex, as indicated by the considerably higher serum zinc level (4.16 ± 0.53 versus 2.56 ± 0.45 mg/L) and intestinal ZIP4, MT1, and DMT1 gene expression than ZnCl2. Further treatment of different zinc channel inhibitors and CETSA demonstrated the direct interaction of zinc-sucrose complex with ZIP4 protein and ZIP4-mediated cellular transport of zinc-sucrose complex. These findings provide a novel insight into the zinc absorption-promoting mechanism of zinc-sucrose complex, which could be used as an ingredient in functional foods to treat zinc deficiency.
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Affiliation(s)
- Nan Li
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, Jiangxi, P. R. China
| | - Ruiyan Wang
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, Jiangxi, P. R. China
| | - Zeyuan Deng
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, Jiangxi, P. R. China
- Institute for Advanced Study, University of Nanchang, Nanchang 330031, Jiangxi, P. R. China
| | - Jianqun Zhou
- Nanning Zeweier Feed Co., Ltd., Nanning 530221, P. R. China
| | - Wenwen Li
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, Jiangxi, P. R. China
| | - Qian Du
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, Jiangxi, P. R. China
| | - Liufeng Zheng
- State Key Laboratory of Food Science and Resources, Nanchang University, Nanchang 330047, Jiangxi, P. R. China
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Kitala K, Tanski D, Godlewski J, Krajewska-Włodarczyk M, Gromadziński L, Majewski M. Copper and Zinc Particles as Regulators of Cardiovascular System Function-A Review. Nutrients 2023; 15:3040. [PMID: 37447366 DOI: 10.3390/nu15133040] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2023] [Revised: 06/30/2023] [Accepted: 07/03/2023] [Indexed: 07/15/2023] Open
Abstract
Copper and zinc are micronutrients that play a crucial role in many cellular pathways, act as cofactors in enzymatic systems, and hence, modulate enzyme activity. The regulation of these elements in homeostasis is precisely controlled by various mechanisms. Superoxide dismutase (SOD) is an enzyme requiring both copper and zinc for proper functioning. Additionally, there is an interaction between the concentrations of copper and zinc. Dietary ingestion of large amounts of zinc augments intestinal absorption of this trace element, resulting in copper deficiency secondary to zinc excess. The presence of an overabundance of copper and zinc has a detrimental impact on the cardiovascular system; however, the impact on vascular contractility varies. Copper plays a role in the modulation of vascular remodeling in the cardiac tissue, and the phenomenon of cuproptosis has been linked to the pathogenesis of coronary artery disease. The presence of copper has an observable effect on the vasorelaxation mediated by nitric oxide. The maintenance of proper levels of zinc within an organism influences SOD and is essential in the pathogenesis of myocardial ischemia/reperfusion injury. Recently, the effects of metal nanoparticles have been investigated due to their unique characteristics. On the other hand, dietary introduction of metal nanoparticles may result in vascular dysfunction, oxidative stress, and cellular DNA damage. Copper and zinc intake affect cardiovascular function, but more research is needed.
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Affiliation(s)
- Klaudia Kitala
- Department of Pharmacology and Toxicology, Faculty of Medicine, University of Warmia and Mazury in Olsztyn, 10-082 Olsztyn, Poland
| | - Damian Tanski
- Department of Human Histology and Embryology, Faculty of Medicine, University of Warmia and Mazury in Olsztyn, 10-082 Olsztyn, Poland
| | - Janusz Godlewski
- Department of Human Histology and Embryology, Faculty of Medicine, University of Warmia and Mazury in Olsztyn, 10-082 Olsztyn, Poland
| | - Magdalena Krajewska-Włodarczyk
- Department of Mental and Psychosomatic Diseases, Faculty of Medicine, University of Warmia and Mazury in Olsztyn, 10-082 Olsztyn, Poland
| | - Leszek Gromadziński
- Department of Cardiology and Internal Medicine, Faculty of Medicine, University of Warmia and Mazury in Olsztyn, 10-082 Olsztyn, Poland
| | - Michał Majewski
- Department of Pharmacology and Toxicology, Faculty of Medicine, University of Warmia and Mazury in Olsztyn, 10-082 Olsztyn, Poland
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11
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Jackson C, Kolba N, Tako E. Assessing the Interactions between Zinc and Vitamin A on Intestinal Functionality, Morphology, and the Microbiome In Vivo ( Gallus gallus). Nutrients 2023; 15:2754. [PMID: 37375657 DOI: 10.3390/nu15122754] [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: 05/23/2023] [Revised: 06/09/2023] [Accepted: 06/13/2023] [Indexed: 06/29/2023] Open
Abstract
Dietary deficiencies in zinc (Zn) and vitamin A (VA) are among the leading micronutrient deficiencies globally and previous research has proposed a notable interaction between Zn and VA physiological status. This study aimed to assess the effects of zinc and vitamin A (isolated and combined) on intestinal functionality and morphology, and the gut microbiome (Gallus gallus). The study included nine treatment groups (n~11)-no-injection (NI); H2O; 0.5% oil; normal zinc (40 mg/kg ZnSO4) (ZN); low zinc (20 mg/kg) (ZL); normal retinoid (1500 IU/kg retinyl palmitate) (RN); low retinoid (100 IU/kg) (RL); normal zinc and retinoid (40 mg/kg; 1500 IU/kg) (ZNRN); low zinc and retinoid (ZLRL) (20 mg/kg; 100 IU/kg). Samples were injected into the amniotic fluid of the fertile broiler eggs. Tissue samples were collected upon hatch to target biomarkers. ZLRL reduced ZIP4 gene expression and upregulated ZnT1 gene expression (p < 0.05). Duodenal surface area increased the greatest in RL compared to RN (p < 0.01), and ZLRL compared to ZNRN (p < 0.05). All nutrient treatments yielded shorter crypt depths (p < 0.01). Compared to the oil control, ZLRL and ZNRN reduced (p < 0.05) the cecal abundance of Bifidobacterium and Clostridium genera (p < 0.05). These results suggest a potentially improved intestinal epithelium proceeding with Zn and VA intra-amniotic administration. Intestinal functionality and gut bacteria were modulated. Further research should characterize long-term responses and the microbiome profile.
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Affiliation(s)
- Cydney Jackson
- Department of Food Science, Cornell University, Ithaca, NY 14850, USA
| | - Nikolai Kolba
- Department of Food Science, Cornell University, Ithaca, NY 14850, USA
| | - Elad Tako
- Department of Food Science, Cornell University, Ithaca, NY 14850, USA
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12
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Nakagawa N, Fujisawa Y, Xiang H, Kitamura H, Nishida K. Inhibitory Effect of Zinc on Colorectal Cancer by Granzyme B Transcriptional Regulation in Cytotoxic T Cells. Int J Mol Sci 2023; 24:ijms24119457. [PMID: 37298408 DOI: 10.3390/ijms24119457] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Revised: 05/24/2023] [Accepted: 05/26/2023] [Indexed: 06/12/2023] Open
Abstract
Zinc is one of the essential trace elements and is involved in various functions in the body. Zinc deficiency is known to cause immune abnormalities, but the mechanism is not fully understood. Therefore, we focused our research on tumor immunity to elucidate the effect of zinc on colorectal cancer and its mechanisms. Mice were treated with azoxymethane (AOM) and dextran sodium sulfate (DSS) to develop colorectal cancer, and the relationship between zinc content in the diet and the number and area of tumors in the colon was observed. The number of tumors in the colon was significantly higher in the no-zinc-added group than in the normal zinc intake group, and about half as many in the high-zinc-intake group as in the normal-zinc-intake group. In T-cell-deficient mice, the number of tumors in the high-zinc-intake group was similar to that in the normal-zinc-intake group, suggesting that the inhibitory effect of zinc was dependent on T cells. Furthermore, we found that the amount of granzyme B transcript released by cytotoxic T cells upon antigen stimulation was significantly increased by the addition of zinc. We also showed that granzyme B transcriptional activation by zinc addition was dependent on calcineurin activity. In this study, we have shown that zinc exerts its tumor-suppressive effect by acting on cytotoxic T cells, the center of cellular immunity, and increases the transcription of granzyme B, one of the key molecules in tumor immunity.
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Affiliation(s)
- Naoya Nakagawa
- Laboratory of Immune Regulation, Graduate School of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka 513-8670, Japan
| | - Yutaka Fujisawa
- Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka 513-8670, Japan
| | - Huihui Xiang
- Division of Functional Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan
| | - Hidemitsu Kitamura
- Division of Functional Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan
- Department of Biomedical Engineering, Faculty of Science and Engineering, Toyo University, Kawagoe 350-8585, Japan
| | - Keigo Nishida
- Laboratory of Immune Regulation, Graduate School of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka 513-8670, Japan
- Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka 513-8670, Japan
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13
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Marrone G, Serra A, Miele L, Biolato M, Liguori A, Grieco A, Gasbarrini A. Branched chain amino acids in hepatic encephalopathy and sarcopenia in liver cirrhosis: Evidence and uncertainties. World J Gastroenterol 2023; 29:2905-2915. [PMID: 37274800 PMCID: PMC10237095 DOI: 10.3748/wjg.v29.i19.2905] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2022] [Revised: 01/24/2023] [Accepted: 04/20/2023] [Indexed: 05/16/2023] Open
Abstract
Liver cirrhosis is commonly associated with nutritional alterations, reported in 20% of patients with compensated disease and over 60% of patients with decompensated cirrhosis. Nutritional disturbances are associated with a worse prognosis and increased risk of complication. Serum levels of branched-chain amino acids (BCAAs) are decreased in patients with liver cirrhosis. The imbalance of amino acids levels has been suggested to be associated with the development of complications, such as hepatic encephalopathy and sarcopenia, and to affect the clinical presentation and prognosis of these patients. Several studies investigated the efficacy of BCAAs supplementation as a therapeutic option in liver cirrhosis, but uncertainties remain about the real efficacy, the best route of administration, and dosage.
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Affiliation(s)
- Giuseppe Marrone
- Medical and Surgical Sciences, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Amato Serra
- Medical and Surgical Sciences, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Luca Miele
- Medical and Surgical Sciences, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Marco Biolato
- Medical and Surgical Sciences, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Antonio Liguori
- Medical and Surgical Sciences, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Antonio Grieco
- Medical and Surgical Sciences, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
| | - Antonio Gasbarrini
- Medical and Surgical Sciences, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Università Cattolica del Sacro Cuore, Rome 00168, Italy
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14
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Katimba HA, Wang R, Cheng C, Zhang Y, Lu W, Ma Y. Zinc Absorption & Homeostasis in the Human Body: A General Overview. FOOD REVIEWS INTERNATIONAL 2023. [DOI: 10.1080/87559129.2023.2195188] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/30/2023]
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15
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Elwyn R, Mitchell J, Kohn MR, Driver C, Hay P, Lagopoulos J, Hermens DF. Novel ketamine and zinc treatment for anorexia nervosa and the potential beneficial interactions with the gut microbiome. Neurosci Biobehav Rev 2023; 148:105122. [PMID: 36907256 DOI: 10.1016/j.neubiorev.2023.105122] [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: 11/01/2022] [Revised: 03/04/2023] [Accepted: 03/07/2023] [Indexed: 03/13/2023]
Abstract
Anorexia nervosa (AN) is a severe illness with diverse aetiological and maintaining contributors including neurobiological, metabolic, psychological, and social determining factors. In addition to nutritional recovery, multiple psychological and pharmacological therapies and brain-based stimulations have been explored; however, existing treatments have limited efficacy. This paper outlines a neurobiological model of glutamatergic and γ-aminobutyric acid (GABA)-ergic dysfunction, exacerbated by chronic gut microbiome dysbiosis and zinc depletion at a brain and gut level. The gut microbiome is established early in development, and early exposure to stress and adversity contribute to gut microbial disturbance in AN, early dysregulation to glutamatergic and GABAergic networks, interoceptive impairment, and inhibited caloric harvest from food (e.g., zinc malabsorption, competition for zinc ions between gut bacteria and host). Zinc is a key part of glutamatergic and GABAergic networks, and also affects leptin and gut microbial function; systems dysregulated in AN. Low doses of ketamine in conjunction with zinc, could provide an efficacious combination to act on NMDA receptors and normalise glutamatergic, GABAergic and gut function in AN.
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Affiliation(s)
- Rosiel Elwyn
- Thompson Institute, University of the Sunshine Coast, Birtinya, QLD, Australia; SouthWest Sydney Local Health District, Liverpool Hospital, Liverpool, NSW, Australia.
| | - Jules Mitchell
- Thompson Institute, University of the Sunshine Coast, Birtinya, QLD, Australia; SouthWest Sydney Local Health District, Liverpool Hospital, Liverpool, NSW, Australia
| | - Michael R Kohn
- AYA Medicine Westmead Hospital, CRASH (Centre for Research into Adolescent's Health) Western Sydney Local Health District, Sydney University, Australia; SouthWest Sydney Local Health District, Liverpool Hospital, Liverpool, NSW, Australia
| | - Christina Driver
- Thompson Institute, University of the Sunshine Coast, Birtinya, QLD, Australia; SouthWest Sydney Local Health District, Liverpool Hospital, Liverpool, NSW, Australia
| | - Phillipa Hay
- Translational Health Research Institute (THRI) School of Medicine, Western Sydney University, Campbelltown, NSW, Australia; SouthWest Sydney Local Health District, Liverpool Hospital, Liverpool, NSW, Australia
| | - Jim Lagopoulos
- Thompson Institute, University of the Sunshine Coast, Birtinya, QLD, Australia; SouthWest Sydney Local Health District, Liverpool Hospital, Liverpool, NSW, Australia
| | - Daniel F Hermens
- Thompson Institute, University of the Sunshine Coast, Birtinya, QLD, Australia; SouthWest Sydney Local Health District, Liverpool Hospital, Liverpool, NSW, Australia
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16
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Lin D, Medeiros DM. The microbiome as a major function of the gastrointestinal tract and its implication in micronutrient metabolism and chronic diseases. Nutr Res 2023; 112:30-45. [PMID: 36965327 DOI: 10.1016/j.nutres.2023.02.007] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Revised: 02/22/2023] [Accepted: 02/25/2023] [Indexed: 03/06/2023]
Abstract
The composition and function of microbes harbored in the human gastrointestinal lumen have been underestimated for centuries because of the underdevelopment of nucleotide sequencing techniques and the lack of humanized gnotobiotic models. Now, we appreciate that the gut microbiome is an integral part of the human body and exerts considerable roles in host health and diseases. Dietary factors can induce changes in the microbial community composition, metabolism, and function, thereby altering the host immune response, and consequently, may influence disease risks. An imbalance of gut microbiome homeostasis (i.e., dysbiosis) has been linked to several chronic diseases, such as inflammatory bowel diseases, obesity, and diabetes. Remarkable progress has recently been made in better understanding the extent to which the influence of the diet-microbiota interaction on host health outcomes in both animal models and human participants. However, the exact causality of the gut microbiome on the development of diseases is still controversial. In this review, we will briefly describe the general structure and function of the intestine and the process of nutrient absorption in humans. This is followed by a summarization of the recent updates on interactions between gut microbiota and individual micronutrients, including carotenoids, vitamin A, vitamin D, vitamin C, folate, iron, and zinc. In the opinion of the authors, these nutrients were identified as representative of vitamins and minerals with sufficient research on their roles in the microbiome. The host responses to the gut microbiome will also be discussed. Future direction in microbiome research, for example, precision microbiome, will be proposed.
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Affiliation(s)
- Dingbo Lin
- Department of Nutritional Sciences, Oklahoma State University, Stillwater, OK 74078.
| | - Denis M Medeiros
- Division of Molecular Biology and Biochemistry, University of Missouri-Kansas City, Kansas City, MO 64108
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17
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Sugimoto R, Tanaka Y, Senju T, Morita Y, Lee L, Hijioka M, Hisano T, Furukawa M. Serum zinc levels in cancer patients are low and difficult to elevate when complicated by liver cirrhosis: A retrospective study. Medicine (Baltimore) 2023; 102:e32703. [PMID: 36701704 PMCID: PMC9857535 DOI: 10.1097/md.0000000000032703] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/27/2023] Open
Abstract
In this study, we analyzed blood zinc concentration in patients with various cancer types and the degree of improvement in relation to the underlying disease following treatment with zinc preparations. Serum zinc levels of 530 cancer patients whose blood zinc levels were measured at our hospital from 2016 to 2021 were retrospectively examined in accordance with the primary disease. Changes in zinc levels were analyzed in 155 patients whose zinc levels had been measured on 2 or more occasions in accordance with whether they had received zinc preparations. In addition, the concentration course of zinc before and after zinc formulation administration in 73 patients was examined in accordance with the presence or absence of liver cirrhosis complications. Mean serum zinc levels were below normal in all carcinomas measured, and zinc levels were significantly lower in cirrhosis-hepatocarcinoma cases than in other primary disease cases. Furthermore, serum zinc levels in patients who did not receive zinc preparations decreased significantly over time. In patients who received zinc preparations, the elevated levels of zinc after treatment were significantly lower in patients with cirrhosis than in those without cirrhosis. There was a weak inverse correlation between pre-dose zinc concentration and increased zinc concentration in patients with cirrhosis. In the analysis of covariance, the presence of liver cirrhosis was predominantly correlated with elevated zinc per dose. In summary, serum zinc levels in cancer patients are low and especially low in cancer patients with liver cirrhosis compared with those without cirrhosis after the administration of zinc preparations.
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Affiliation(s)
- Rie Sugimoto
- Department of Hepato-Biliary-Pancreatology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan
- * Correspondence: Rie Sugimoto, Department of Hepato-Biliary-Pancreatology, National Hospital Organization Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka 811-1395, Japan (e-mail: )
| | - Yuki Tanaka
- Department of Hepato-Biliary-Pancreatology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan
| | - Takeshi Senju
- Department of Hepato-Biliary-Pancreatology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan
| | - Yusuke Morita
- Department of Hepato-Biliary-Pancreatology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan
| | - Lingaku Lee
- Department of Hepato-Biliary-Pancreatology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan
| | - Masayuki Hijioka
- Department of Hepato-Biliary-Pancreatology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan
| | - Terumasa Hisano
- Department of Hepato-Biliary-Pancreatology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan
| | - Masayuki Furukawa
- Department of Hepato-Biliary-Pancreatology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan
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18
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The Significance of Zinc in Patients with Chronic Liver Disease. Nutrients 2022; 14:nu14224855. [PMID: 36432541 PMCID: PMC9692841 DOI: 10.3390/nu14224855] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2022] [Revised: 11/10/2022] [Accepted: 11/13/2022] [Indexed: 11/18/2022] Open
Abstract
Zinc is an essential trace element for the maintenance of life because it acts as a center of activity or cofactor for hundreds of enzymes. Zinc deficiency causes a variety of symptoms, including anemia, dermatitis, stomatitis, alopecia, bedsores, decreased appetite, impaired growth, gonadal dysfunction, susceptibility to infection, and taste disorders, etc. In March 2017, zinc acetate hydrate, which had been approved for Wilson disease in Japan, received an additional indication for hypozincemia. Hypozincemia is frequently observed in patients with chronic liver disease (CLD), especially cirrhosis, and it has recently been shown that hypozincemia is closely related to the development of liver fibrosis and increased risk of liver carcinogenesis, in addition to the appearance of various subjective symptoms. Moreover, hypozincemia in CLD may be associated with sarcopenia (i.e., decrease in muscle strength and muscle mass) and frailty (i.e., vulnerability), which receive much attention these days. It is assumed that treatment with zinc acetate hydrate will become widespread in patients with CLD. Zinc acetate hydrate may also have potential for improving sarcopenia in patients with CLD. This review primarily outlines the significance of zinc in patients with CLD.
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19
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Byrne L, Murphy RA. Relative Bioavailability of Trace Minerals in Production Animal Nutrition: A Review. Animals (Basel) 2022; 12:1981. [PMID: 35953970 PMCID: PMC9367456 DOI: 10.3390/ani12151981] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Revised: 07/22/2022] [Accepted: 08/01/2022] [Indexed: 11/16/2022] Open
Abstract
The importance of dietary supplementation of animal feeds with trace minerals is irrefutable, with various forms of both organic and inorganic products commercially available. With advances in research techniques, and data obtained from both in-vitro and in-vivo studies in recent years, differences between inorganic and organic trace minerals have become more apparent. Furthermore, differences between specific organic mineral types can now be identified. Adhering to PRISMA guidelines for systematic reviews, we carried out an extensive literature search on previously published studies detailing performance responses to trace minerals, in addition to their corresponding relative bioavailability values. This review covers four of the main trace minerals included in feed: copper, iron, manganese and zinc, and encompasses the different types of organic and inorganic products commercially available. Their impact from environmental, economic, and nutritional perspectives are discussed, along with the biological availability of various mineral forms in production animals. Species-specific sections cover ruminants, poultry, and swine. Extensive relative bioavailability tables cover values for all trace mineral products commercially available, including those not previously reviewed in earlier studies, thereby providing a comprehensive industry reference guide. Additionally, we examine reasons for variance in reported relative bioavailability values, with an emphasis on accounting for data misinterpretation.
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Affiliation(s)
- Laurann Byrne
- Alltech Bioscience Centre, Summerhill Road, Dunboyne, A86 X006 Co. Meath, Ireland
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20
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Hussain A, Jiang W, Wang X, Shahid S, Saba N, Ahmad M, Dar A, Masood SU, Imran M, Mustafa A. Mechanistic Impact of Zinc Deficiency in Human Development. Front Nutr 2022; 9:717064. [PMID: 35356730 PMCID: PMC8959901 DOI: 10.3389/fnut.2022.717064] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2021] [Accepted: 01/31/2022] [Indexed: 12/15/2022] Open
Abstract
Zinc (Zn) deficiency in humans is an emerging global health issue affecting approximately two billion people across the globe. The situation prevails due to the intake of Zn deficient grains and vegetables worldwide. Clinical identification of Zn deficiency in humans remains problematic because the symptoms do not appear until impair the vital organs, such as the gastrointestinal track, central nervous system, immune system, skeletal, and nervous system. Lower Zn body levels are also responsible for multiple physiological disorders, such as apoptosis, organs destruction, DNA injuries, and oxidative damage to the cellular components through reactive oxygen species (ROS). The oxidative damage causes chronic inflammation lead toward several chronic diseases, such as heart diseases, cancers, alcohol-related malady, muscular contraction, and neuro-pathogenesis. The present review focused on the physiological and growth-related changes in humans under Zn deficient conditions, mechanisms adopted by the human body under Zn deficiency for the proper functioning of the body systems, and the importance of nutritional and nutraceutical approaches to overcome Zn deficiency in humans and concluded that the biofortified food is the best source of Zn as compared to the chemical supplementation to avoid their negative impacts on human.
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Affiliation(s)
- Azhar Hussain
- Department of Soil Science, The Islamia Diversity of Bahawalpur, Bahawalpur, Pakistan
| | - Wenting Jiang
- College of Life Sciences, Yan'an University, Yan'an, China
| | - Xiukang Wang
- College of Life Sciences, Yan'an University, Yan'an, China
| | - Shumaila Shahid
- Department of Soil Science, The Islamia Diversity of Bahawalpur, Bahawalpur, Pakistan
| | - Noreena Saba
- Qaid-e-Azam Medical College, Bahawal Victoria Hospital, Bahawalpur, Pakistan
| | - Maqshoof Ahmad
- Department of Soil Science, The Islamia Diversity of Bahawalpur, Bahawalpur, Pakistan
| | - Abubakar Dar
- Department of Soil Science, The Islamia Diversity of Bahawalpur, Bahawalpur, Pakistan
| | - Syed Usama Masood
- Clinical Fellow Pediatric Nephrology, Children Hospital and Institute of Child Health Multan, Multan, Pakistan
| | | | - Adnan Mustafa
- Faculty of Chemistry, Institute of Chemistry and Technology of Environmental Protection, Brno University of Technology, Brno, Czechia
- Department of Agrochemistry, Soil Science, Microbiology and Plant Nutrition (FA), Mendel University, Brno, Czechia
- Institute of Environmental Studies, Charles University Prague, Prague, Czechia
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21
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Zyambo K, Hodges P, Chandwe K, Mweetwa M, Westcott J, Krebs NF, Amadi B, Kelly P. Reduced Fractional Absorption of Zinc in Children With Environmental Enteropathy in Zambia. J Pediatr Gastroenterol Nutr 2022; 74:277-283. [PMID: 34469927 DOI: 10.1097/mpg.0000000000003292] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
OBJECTIVES We measured fractional absorption of zinc (FAZ) in children with environmental enteropathy (EE) and carried out transcriptomic analysis of biopsies from these children in order to compare FAZ to histology of intestinal biopsies, expression of zinc transporter genes, and biomarkers of enteropathy. METHODS Fractional absorption of a standardized aqueous dose of zinc was measured by a dual isotope ratio technique in a cohort of children ages between 9 and 24 months in Lusaka, Zambia, who all had non-responsive stunting. Gene expression analysis was carried out on biopsies through RNA sequencing using an Illumina HiSeq2000 platform. RESULTS All 33 children had histological features of environmental enteropathy and plasma zinc concentrations below the lower limit of normal. Measured FAZ ranged from 0.18 to 0.93; all values >0.55 were observed in girls. FAZ was negatively correlated with faecal myeloperoxidase (MPO) (ρ = -0.51, n = 17; P = 0.04) and faecal calprotectin (ρ = -0.50, n = 16; P = 0.05), but not blood biomarkers. Of 41 genes with known roles in zinc metabolism, only three metallothionein genes were significantly correlated with FAZ. CONCLUSIONS Zinc homeostasis is impaired in children with environmental enteropathy, and was inversely correlated with mucosal inflammation. Reduced FAZ without specific changes in expression of most zinc transporter genes could be explained by reduced absorptive surface area due to villus/microvillus atrophy.
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Affiliation(s)
- Kanekwa Zyambo
- Tropical Gastroenterology & Nutrition group, University of Zambia School of Medicine, Lusaka, Zambia
| | - Phoebe Hodges
- Tropical Gastroenterology & Nutrition group, University of Zambia School of Medicine, Lusaka, Zambia
- Blizard Institute, Barts & The London School of Medicine, Queen Mary University of London, London, UK
| | - Kanta Chandwe
- Tropical Gastroenterology & Nutrition group, University of Zambia School of Medicine, Lusaka, Zambia
| | - Monica Mweetwa
- Tropical Gastroenterology & Nutrition group, University of Zambia School of Medicine, Lusaka, Zambia
| | - Jamie Westcott
- Section of Pediatric Nutrition, University of Colorado School of Medicine, Aurora, CO
| | - Nancy F Krebs
- Section of Pediatric Nutrition, University of Colorado School of Medicine, Aurora, CO
| | - Beatrice Amadi
- Tropical Gastroenterology & Nutrition group, University of Zambia School of Medicine, Lusaka, Zambia
| | - Paul Kelly
- Tropical Gastroenterology & Nutrition group, University of Zambia School of Medicine, Lusaka, Zambia
- Blizard Institute, Barts & The London School of Medicine, Queen Mary University of London, London, UK
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22
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Shkembi B, Huppertz T. Influence of Dairy Products on Bioavailability of Zinc from Other Food Products: A Review of Complementarity at a Meal Level. Nutrients 2021; 13:4253. [PMID: 34959808 PMCID: PMC8705257 DOI: 10.3390/nu13124253] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2021] [Revised: 11/24/2021] [Accepted: 11/25/2021] [Indexed: 11/16/2022] Open
Abstract
In this paper, we reviewed the role of dairy products in dietary zinc absorption. Dairy products can have a reasonable contribution for dietary zinc intake in Western diets, where dairy consumption is high. However, the co-ingestion of dairy products can also improve zinc absorption from other food products. Such improvements have been observed when dairy products (e.g., milk or yoghurt) were ingested together with food such as rice, tortillas or bread products, all of which are considered to be high-phytate foods with low inherent zinc absorption. For foods low in phytate, the co-ingestion of dairy products did not improve zinc absorption. Improved zinc absorption of zinc from high-phytate foods following co-ingestion with dairy products may be related to the beneficial effects of the citrate and phosphopeptides present in dairy products. Considering that the main dietary zinc sources in areas in the world where zinc deficiency is most prevalent are typically high in phytate, the inclusion of dairy products in meals may be a viable dietary strategy to improve zinc absorption.
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Affiliation(s)
- Blerina Shkembi
- Food Quality & Design Group, Wageningen University & Research, 6708 PB Wageningen, The Netherlands;
| | - Thom Huppertz
- Food Quality & Design Group, Wageningen University & Research, 6708 PB Wageningen, The Netherlands;
- FrieslandCampina, 3818 LE Amersfoort, The Netherlands
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23
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Cortez NE, Mackenzie GG. Ketogenic Diets in Pancreatic Cancer and Associated Cachexia: Cellular Mechanisms and Clinical Perspectives. Nutrients 2021; 13:nu13093202. [PMID: 34579079 PMCID: PMC8471358 DOI: 10.3390/nu13093202] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Revised: 09/06/2021] [Accepted: 09/10/2021] [Indexed: 12/15/2022] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and extremely therapy-resistant cancer. It is estimated that up to 80% of PDAC patients present with cachexia, a multifactorial disorder characterized by the involuntary and ongoing wasting of skeletal muscle that affects therapeutic response and survival. During the last decade, there has been an increased interest in exploring dietary interventions to complement the treatment of PDAC and associated cachexia. Ketogenic diets (KDs) have gained attention for their anti-tumor potential. Characterized by a very low carbohydrate, moderate protein, and high fat composition, this diet mimics the metabolic changes that occur in fasting. Numerous studies report that a KD reduces tumor growth and can act as an adjuvant therapy in various cancers, including pancreatic cancer. However, research on the effect and mechanisms of action of KDs on PDAC-associated cachexia is limited. In this narrative review, we summarize the evidence of the impact of KDs in PDAC treatment and cachexia mitigation. Furthermore, we discuss key cellular mechanisms that explain KDs’ potential anti-tumor and anti-cachexia effects, focusing primarily on reprogramming of cell metabolism, epigenome, and the gut microbiome. Finally, we provide a perspective on future research needed to advance KDs into clinical use.
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24
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Cardoso D, Romeo A, Durosoy S, Meme N, Chevalier Y, Narcy A. Effect of the physicochemical properties of zinc oxide sources on their bioavailability in broilers. Br Poult Sci 2021; 62:846-851. [PMID: 34114920 DOI: 10.1080/00071668.2021.1940862] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
1. The bioavailability of a trace mineral source is related to its intestinal solubility (bioaccessibility), which in turn is determined by its physicochemical properties. It is still not clear which characteristics are more relevant in affecting solubility and bioavailability of mineral sources. Zinc oxide (ZnO) is a common feed additive used to supplement zinc in the diet of monogastric animals. However, different sources have shown variable responses on animal bioavailability.2. This study hypothesised that different sources of feed grade ZnO have various physicochemical features that lead to distinct bioavailability values. Feed grade ZnO samples collected from the feed industry worldwide were characterised for their physicochemical features and tested in broilers to allow bioavailability determined.3. A total of 135 male Cobb broiler chickens were fed a standard starter diet from day 1 after hatching up to d 7. At d 8, animals were allocated in individual cages and fed one of the following dietary treatments during 15 days: a basal diet with 23.5 ppm of zinc and seven test diets with supplemented ZnO or zinc sulphate (ZnSO4) at 6 or 12 ppm.4. Different sources of ZnO showed an effect of solubility in the stomach and supplementation influenced total Zn levels in the ileum. The bioavailability of the different sources varied from 49% to 160% in relation to ZnSO4. Aggregate size of particles seems to explain most of the variability in the bioavailability of the different sources tested in broilers. In conclusion, physicochemical properties of ZnO can partly explain the variability observed in terms of biological value.
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Affiliation(s)
- D Cardoso
- LAGEPP, CNRS UMR 507, University of Lyon, Villeurbanne, France.,UMR BOA, INRAE, Université de Tours, Nouzilly, France.,R&D Department, Animine, Annecy, France
| | - A Romeo
- R&D Department, Animine, Annecy, France
| | - S Durosoy
- R&D Department, Animine, Annecy, France
| | - N Meme
- UMR BOA, INRAE, Université de Tours, Nouzilly, France
| | - Y Chevalier
- LAGEPP, CNRS UMR 507, University of Lyon, Villeurbanne, France
| | - A Narcy
- UMR BOA, INRAE, Université de Tours, Nouzilly, France
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Pizzagalli MD, Bensimon A, Superti‐Furga G. A guide to plasma membrane solute carrier proteins. FEBS J 2021; 288:2784-2835. [PMID: 32810346 PMCID: PMC8246967 DOI: 10.1111/febs.15531] [Citation(s) in RCA: 186] [Impact Index Per Article: 46.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2020] [Revised: 08/07/2020] [Accepted: 08/17/2020] [Indexed: 12/13/2022]
Abstract
This review aims to serve as an introduction to the solute carrier proteins (SLC) superfamily of transporter proteins and their roles in human cells. The SLC superfamily currently includes 458 transport proteins in 65 families that carry a wide variety of substances across cellular membranes. While members of this superfamily are found throughout cellular organelles, this review focuses on transporters expressed at the plasma membrane. At the cell surface, SLC proteins may be viewed as gatekeepers of the cellular milieu, dynamically responding to different metabolic states. With altered metabolism being one of the hallmarks of cancer, we also briefly review the roles that surface SLC proteins play in the development and progression of cancer through their influence on regulating metabolism and environmental conditions.
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Affiliation(s)
- Mattia D. Pizzagalli
- CeMM, Research Center for Molecular Medicine of the Austrian Academy of SciencesViennaAustria
| | - Ariel Bensimon
- CeMM, Research Center for Molecular Medicine of the Austrian Academy of SciencesViennaAustria
| | - Giulio Superti‐Furga
- CeMM, Research Center for Molecular Medicine of the Austrian Academy of SciencesViennaAustria
- Center for Physiology and PharmacologyMedical University of ViennaAustria
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Expression Analysis of Zinc Transporters in Nervous Tissue Cells Reveals Neuronal and Synaptic Localization of ZIP4. Int J Mol Sci 2021; 22:ijms22094511. [PMID: 33925953 PMCID: PMC8123391 DOI: 10.3390/ijms22094511] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Revised: 04/19/2021] [Accepted: 04/23/2021] [Indexed: 12/14/2022] Open
Abstract
In the last years, research has shown that zinc ions play an essential role in the physiology of brain function. Zinc acts as a potent neuromodulatory agent and signaling ions, regulating healthy brain development and the function of both neurons and glial cells. Therefore, the concentration of zinc within the brain and its cells is tightly controlled. Zinc transporters are key regulators of (extra-) cellular zinc levels, and deregulation of zinc homeostasis and zinc transporters has been associated with neurodegenerative and neuropsychiatric disorders. However, to date, the presence of specific family members and their subcellular localization within brain cells have not been investigated in detail. Here, we analyzed the expression of all zinc transporters (ZnTs) and Irt-like proteins (ZIPs) in the rat brain. We further used primary rat neurons and rat astrocyte cell lines to differentiate between the expression found in neurons or astrocytes or both. We identified ZIP4 expressed in astrocytes but significantly more so in neurons, a finding that has not been reported previously. In neurons, ZIP4 is localized to synapses and found in a complex with major postsynaptic scaffold proteins of excitatory synapses. Synaptic ZIP4 reacts to short-term fluctuations in local zinc levels. We conclude that ZIP4 may have a so-far undescribed functional role at excitatory postsynapses.
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Zinc in Dog Nutrition, Health and Disease: A Review. Animals (Basel) 2021; 11:ani11040978. [PMID: 33915721 PMCID: PMC8066201 DOI: 10.3390/ani11040978] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 03/11/2021] [Accepted: 03/24/2021] [Indexed: 12/27/2022] Open
Abstract
Simple Summary This work compiles the current state of knowledge regarding zinc requirements of healthy dogs and biomarkers of zinc status. To ensure an adequate zinc status, it is important to know the zinc content of foods and their bioavailability to assess the need and the ideal supplementation strategy regarding levels and sources of additives in complete dog foods. As zinc is required for enzymatic, structural, and regulatory functions in the animal body, its nutritional status has been associated with several pathologies that may be due to, or exacerbated by, a deficit of dietary zinc supply. Abstract Zinc is an essential trace element, required for enzymatic, structural, and regulatory functions. As body reserves are scarce, an adequate zinc status relies on proper dietary supply and efficient homeostasis. Several biomarkers have been proposed that enable the detection of poor zinc status, but more sensitive and specific ones are needed to detect marginal deficiencies. The zinc content of commercial dry dog foods has great variability, with a more frequent non-compliance with the maximum authorized limit than with the nutritional requirement. The bioavailability of dietary zinc also plays a crucial role in ensuring an adequate zinc status. Despite controversial results, organic zinc sources have been considered more bioavailable than inorganic sources, albeit the zinc source effect is more evident after a restriction period of dietary zinc. Many disorders have been associated with inadequate zinc status, not being clear whether the occurrence of the disease is the consequence or the cause. This review presents data on zinc requirements and biomarkers for zinc status, that can be applied for the development of supplementation strategies of zinc in complete pet foods. Moreover, it provides an understanding of the role zinc plays in the health of dogs, and how altered zinc status affects diseases in dogs.
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Unal O, Baltaci AK, Mogulkoc R, Avunduk MC. Effect of pinealectomy and melatonin supplementation on metallothionein, ZnT2, ZIP2, ZIP4 and zinc levels in rat small intestine. Biotech Histochem 2021; 96:623-635. [PMID: 33615931 DOI: 10.1080/10520295.2021.1885738] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2022] Open
Abstract
We investigated the relations among levels of metallothionein (MT); zinc (Zn) transport proteins, ZnT2, ZIP2 (ZRT and IRT-like proteins); and ZIP4, which enable Zn absorption in the small intestine of rats. We also investigated tissue Zn levels in the small intestine. We used four groups of adult male rats: group 1, control; group 2, pinealectomy (Px); group 3, Px + melatonin (MEL); group 4, MEL only. Animals in groups 3 and 4 were administered 5 mg/kg/day MEL for four weeks. At the end of the study, all animals were sacrificed and samples of duodenum, jejunum and ileum were harvested to analyze ZnT2, ZIP2, ZIP4 and MT levels using immunohistochemistry, and tissue Zn levels were measured by atomic absorption spectrophotometry. The lowest ZnT2 levels in the duodenum, jejunum and ileum, and the lowest ZIP2 levels in the duodenum and ileum were found in group 2. The lowest ZIP4 levels were found in the duodenum and jejunum, and the lowest MT levels in the duodenum and ileum were found in group 2. The highest MT values in the ileum were found in group 4. We found that ZnT2, ZIP2, ZIP4 and MT levels were reduced in the ileum compared to controls following Px, but levels approached control values after MEL administration. By its effects on ZnT2, ZIP2, ZIP4 and MT levels, MEL participates in the absorption of Zn in the rat small intestine.
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Affiliation(s)
- Omer Unal
- Faculty of Medicine, Department of Physiology, Selcuk University, Konya, Turkey
| | | | - Rasim Mogulkoc
- Faculty of Medicine, Department of Physiology, Selcuk University, Konya, Turkey
| | - Mustafa Cihat Avunduk
- Faculty of Meram Medicine, Department of Pathology, Necmettin Erbakan University, Konya, Turkey
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Li S, De La Cruz J, Hutchens S, Mukhopadhyay S, Criss ZK, Aita R, Pellon-Cardenas O, Hur J, Soteropoulos P, Husain S, Dhawan P, Verlinden L, Carmeliet G, Fleet JC, Shroyer NF, Verzi MP, Christakos S. Analysis of 1,25-Dihydroxyvitamin D 3 Genomic Action Reveals Calcium-Regulating and Calcium-Independent Effects in Mouse Intestine and Human Enteroids. Mol Cell Biol 2020; 41:e00372-20. [PMID: 33139494 PMCID: PMC7849401 DOI: 10.1128/mcb.00372-20] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2020] [Revised: 10/05/2020] [Accepted: 10/24/2020] [Indexed: 01/27/2023] Open
Abstract
Although vitamin D is critical for the function of the intestine, most studies have focused on the duodenum. We show that transgenic expression of the vitamin D receptor (VDR) only in the distal intestine of VDR null mice (KO/TG mice) results in the normalization of serum calcium and rescue of rickets. Although it had been suggested that calcium transport in the distal intestine involves a paracellular process, we found that the 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]-activated genes in the proximal intestine associated with active calcium transport (Trpv6, S100g, and Atp2b1) are also induced by 1,25(OH)2D3 in the distal intestine of KO/TG mice. In addition, Slc30a10, encoding a manganese efflux transporter, was one of the genes most induced by 1,25(OH)2D3 in both proximal and distal intestine. Both villus and crypt were found to express Vdr and VDR target genes. RNA sequence (RNA-seq) analysis of human enteroids indicated that the effects of 1,25(OH)2D3 observed in mice are conserved in humans. Using Slc30a10-/- mice, a loss of cortical bone and a marked decrease in S100g and Trpv6 in the intestine was observed. Our findings suggest an interrelationship between vitamin D and intestinal Mn efflux and indicate the importance of distal intestinal segments to vitamin D action.
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Affiliation(s)
- Shanshan Li
- Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers, The State University of New Jersey, New Jersey Medical School, Newark, New Jersey, USA
| | - Jessica De La Cruz
- Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers, The State University of New Jersey, New Jersey Medical School, Newark, New Jersey, USA
| | - Steven Hutchens
- Division of Pharmacology and Toxicology, College of Pharmacy, Institute for Cellular and Molecular Biology and Institute for Neuroscience, The University of Texas at Austin, Austin, Texas, USA
| | - Somshuvra Mukhopadhyay
- Division of Pharmacology and Toxicology, College of Pharmacy, Institute for Cellular and Molecular Biology and Institute for Neuroscience, The University of Texas at Austin, Austin, Texas, USA
| | - Zachary K Criss
- Integrative Molecular and Biomedical Sciences Graduate Program, Division of Medicine, Baylor College of Medicine, Houston, Texas, USA
| | - Rohit Aita
- Department of Genetics, Rutgers University, New Brunswick, New Jersey, USA
| | | | - Joseph Hur
- Department of Genetics, Rutgers University, New Brunswick, New Jersey, USA
| | - Patricia Soteropoulos
- Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers, The State University of New Jersey, New Jersey Medical School, Newark, New Jersey, USA
- Genomics Center, Rutgers, The State University of New Jersey, New Jersey Medical School, Newark, New Jersey, USA
| | - Seema Husain
- Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers, The State University of New Jersey, New Jersey Medical School, Newark, New Jersey, USA
- Genomics Center, Rutgers, The State University of New Jersey, New Jersey Medical School, Newark, New Jersey, USA
| | - Puneet Dhawan
- Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers, The State University of New Jersey, New Jersey Medical School, Newark, New Jersey, USA
- Genomics Center, Rutgers, The State University of New Jersey, New Jersey Medical School, Newark, New Jersey, USA
| | - Lieve Verlinden
- Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, Leuven, Belgium
| | - Geert Carmeliet
- Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, Leuven, Belgium
| | - James C Fleet
- Department of Nutrition Science, Purdue University, West Lafayette, Indiana, USA
| | - Noah F Shroyer
- Integrative Molecular and Biomedical Sciences Graduate Program, Division of Medicine, Baylor College of Medicine, Houston, Texas, USA
| | - Michael P Verzi
- Department of Genetics, Rutgers University, New Brunswick, New Jersey, USA
| | - Sylvia Christakos
- Department of Microbiology, Biochemistry and Molecular Genetics, Rutgers, The State University of New Jersey, New Jersey Medical School, Newark, New Jersey, USA
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Kwok ML, Meng Q, Hu XL, Chung CT, Chan KM. Whole-transcriptome sequencing (RNA-seq) study of the ZFL zebrafish liver cell line after acute exposure to Cd 2+ ions. AQUATIC TOXICOLOGY (AMSTERDAM, NETHERLANDS) 2020; 228:105628. [PMID: 32971353 DOI: 10.1016/j.aquatox.2020.105628] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Revised: 09/03/2020] [Accepted: 09/06/2020] [Indexed: 06/11/2023]
Abstract
Cadmium (Cd) is a non-essential metal with no known biological function and a broad range of toxic effects in biological systems. We used whole-transcriptome sequencing (RNA-seq) to study the effects of Cd2+ toxicity in zebrafish liver cells, ZFL. The results of an RNA-Seq analysis of ZFL cells exposed to 5, 10 or 20 μM Cd2+ for 4- or 24-h. The differentially expressed genes affected by Cd2+ were analyzed by using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to study the regulated pathways. Cd2+ regulated the expression of genes associated with cellular Cu, Zn, and Fe homeostasis, DNA replication leading to cell cycle arrest and apoptosis, and glutathione metabolism. Cd2+ boosted up the amino acid synthesis, possibly to support the glutathione metabolism for tackling the oxidative stress generated from Cd2+. Cd2+ stimulation was similar to heat or xenobiotics, based on the responses from ZFL such as endoplasmic reticulum stress and protein folding. We linked also those finding of gene activations relating to carcinogenesis of Cd. This paper provides a comprehensive analysis of the expression profiles induced by Cd2+ exposure in ZFL cells, as well as useful insights into the specific toxic effects.
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Affiliation(s)
- Man Long Kwok
- School of Life Sciences, The Chinese University of Hong Kong, Sha Tin., N.T., Hong Kong
| | - Qi Meng
- School of Life Sciences, The Chinese University of Hong Kong, Sha Tin., N.T., Hong Kong
| | - Xue Lei Hu
- School of Life Sciences, The Chinese University of Hong Kong, Sha Tin., N.T., Hong Kong
| | - Chun Ting Chung
- School of Life Sciences, The Chinese University of Hong Kong, Sha Tin., N.T., Hong Kong
| | - King Ming Chan
- School of Life Sciences, The Chinese University of Hong Kong, Sha Tin., N.T., Hong Kong.
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VanValin KR, Genther-Schroeder ON, Carmichael RN, Blank CP, Deters EL, Hartman SJ, Niedermayer EK, Hansen SL. Trace mineral metabolism and nutrient digestibility in lambs supplemented with zinc sulfate during an adrenocorticotropic hormone challenge. Livest Sci 2020. [DOI: 10.1016/j.livsci.2020.104197] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Pre-dialysis serum creatinine as an independent predictor of responsiveness to zinc supplementation among patients on hemodialysis. Clin Exp Nephrol 2020; 24:955-962. [PMID: 32557260 DOI: 10.1007/s10157-020-01911-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2020] [Accepted: 06/01/2020] [Indexed: 10/24/2022]
Abstract
BACKGROUND To investigate whether pre-dialysis level of serum creatinine (SCre) could indicate the responsiveness to zinc supplementation of patients on maintenance hemodialysis (MHD). METHODS We retrospectively reviewed the results of our previous randomized study of 91 patients who had been on MHD and received zinc supplementation with either zinc acetate hydrate (ZAH; zinc, 50 mg/day) or polaprezinc (PPZ; zinc, 34 mg/day). A late response to zinc supplementation was defined as a serum zinc level of < 80 μg/dL three months after the study began. Patients were divided into two groups: late response (serum zinc level < 80 μg/dL) and early response (serum zinc level ≥ 80 μg/dL). Factors independently associated with a late response to zinc supplementation were determined using inverse probability of treatment weighting (IPTW) multivariate logistic analysis. RESULTS Of 91 patients, 86 continued to receive zinc supplementation after three months. The mean pre-dialysis SCre level was 10.0 mg/dL. The number of patients with a late response and response to zinc supplementation was 32 and 54, respectively. There was a significant negative correlation between the pre-dialysis SCre and the Δserum zinc change for 3 months. (r = - 0.284, P = 0.008). IPTW multivariate analysis showed that a pre-dialysis SCre level ≥ 10.0 mg/dL (odds ratio, 3.71; 95% confidence interval; 1.24-11.1, P = 0.022) was an independent factor associated with a late response to zinc supplementation. CONCLUSIONS Pre-dialysis SCre level was independently associated with responsiveness to zinc supplementation after three months in patients on MHD.
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Ozeki I, Yamaguchi M, Suii H, Tatsumi R, Arakawa T, Nakajima T, Kuwata Y. The association between serum zinc levels and subjective symptoms in zinc deficiency patients with chronic liver disease. J Clin Biochem Nutr 2020; 66:253-261. [PMID: 32523253 DOI: 10.3164/jcbn.19-99] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2019] [Accepted: 12/04/2019] [Indexed: 11/22/2022] Open
Abstract
This study aimed to analyze the association between serum zinc levels and major subjective symptoms in zinc deficiency patients with chronic liver disease. 578 patients with chronic liver disease were enrolled. The patients, whose serum zinc level of <80 µg/dl, completed a questionnaire to determine whether they had subjective symptoms of the five conditions (taste disorder, aphthous stomatitis, dermatitis, alopecia, and anorexia). Then, the association between these subjective symptoms and serum zinc levels was analyzed. In total, 193 patients (33.4%) experienced any subjective symptoms. The prevalence of each symptom was as follows: 36 patients with taste disorder (6.2%), 46 with aphthous stomatitis (8.0%), 77 with dermatitis (13.3%), 46 with alopecia (8.0%), and 53 with anorexia (9.2%). In total, 70.8%, 34.1%, and 26.1% patients with serum zinc levels of <40, ≥40 to <60, and ≥60 to <80 µg/dl, respectively, had these symptoms. When zinc deficiency was defined as a serum zinc level of <80 µg/dl, approximately one-third of patients displayed symptoms presumably originating from zinc deficiency. As serum zinc levels decreased, the prevalence of these symptoms increased. Dermatitis, especially, was relevant to zinc.
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Affiliation(s)
- Itaru Ozeki
- Department of Hepatology, Sapporo Kosei General Hospital, Kita 3 Higashi 8, Chuo-ku, Sapporo 060-0033, Japan
| | - Masakatsu Yamaguchi
- Department of Hepatology, Sapporo Kosei General Hospital, Kita 3 Higashi 8, Chuo-ku, Sapporo 060-0033, Japan
| | - Hirokazu Suii
- Department of Hepatology, Sapporo Kosei General Hospital, Kita 3 Higashi 8, Chuo-ku, Sapporo 060-0033, Japan
| | - Ryoji Tatsumi
- Department of Hepatology, Sapporo Kosei General Hospital, Kita 3 Higashi 8, Chuo-ku, Sapporo 060-0033, Japan
| | - Tomohiro Arakawa
- Department of Hepatology, Sapporo Kosei General Hospital, Kita 3 Higashi 8, Chuo-ku, Sapporo 060-0033, Japan
| | - Tomoaki Nakajima
- Department of Hepatology, Sapporo Kosei General Hospital, Kita 3 Higashi 8, Chuo-ku, Sapporo 060-0033, Japan
| | - Yasuaki Kuwata
- Department of Hepatology, Sapporo Kosei General Hospital, Kita 3 Higashi 8, Chuo-ku, Sapporo 060-0033, Japan
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Ozeki I, Nakajima T, Suii H, Tatsumi R, Yamaguchi M, Arakawa T, Kuwata Y, Toyota J, Karino Y. Evaluation of treatment with zinc acetate hydrate in patients with liver cirrhosis complicated by zinc deficiency. Hepatol Res 2020; 50:488-501. [PMID: 31729098 DOI: 10.1111/hepr.13461] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/05/2019] [Revised: 10/24/2019] [Accepted: 11/04/2019] [Indexed: 12/12/2022]
Abstract
AIM In Japan, no zinc preparation had been approved for therapeutic purposes before March 2017. Zinc acetate hydrate was recently approved for the treatment of hypozincemia. We evaluated the efficacy and safety of treatment with zinc acetate hydrate. METHODS A total of 97 patients with cirrhosis complicated by hypozincemia were treated with zinc acetate hydrate, and their serum zinc normalization rates; factors contributing to normalization; changes in blood ammonia levels; branched-chain amino acids-to-tyrosine ratios; levels of albumin, hemoglobin, alkaline phosphatase, serum copper, and iron; incidence of adverse events; improvement in subjective symptoms; and serum zinc levels taken at 3 months post-treatment were determined. RESULTS The cumulative serum zinc normalization rates, when normalization was defined as achievement of a serum zinc level ≥80 μg/dL, after 2, 4, and 6 months of treatment were 64.9%, 80.3%, and 82.5%, respectively. Multivariate analysis identified an albumin level of ≥3.3 g/dL and branched-chain amino acids to tyrosine ratio of ≥3.46 as factors contributing to zinc normalization within 3 months of treatment. Treatment resulted in a significant decrease in blood ammonia and serum copper levels, and significant increases in branched-chain amino acids-to-tyrosine ratios and alkaline phosphatase levels. Seven (7.2%) patients prematurely discontinued treatment due to hypocupremia. By the end of treatment, subjective symptoms had resolved in 46.2% of patients. By 3 months post-treatment, serum zinc levels had reverted to levels close to those at baseline. CONCLUSIONS Treatment with zinc acetate hydrate resulted in normalization of serum zinc levels at a high rate. The main reasons for discontinuation of treatment included hypocupremia.
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Okamoto T, Hatakeyama S, Konishi S, Okita K, Tanaka Y, Imanishi K, Takashima T, Saitoh F, Suzuki T, Ohyama C. Comparison of zinc acetate hydrate and polaprezinc for zinc deficiency in patients on maintenance hemodialysis: A single-center, open-label, prospective randomized study. Ther Apher Dial 2019; 24:568-577. [PMID: 31794152 DOI: 10.1111/1744-9987.13461] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2019] [Revised: 10/30/2019] [Accepted: 12/02/2019] [Indexed: 02/06/2023]
Abstract
The efficacy and safety of zinc acetate hydrate (ZAH) for zinc supplementation in patients on maintenance hemodialysis (MHD) remains unknown. In this prospective, single-center, open-label, parallel-group trial for MHD patients with serum zinc level <70 μg/dL, we compared ZAH (zinc; 50 mg/day) and polaprezinc (PPZ; zinc; 34 mg/day) beyond 6-month administration in a 1:1 randomization manner. The ZAH and PPZ groups had 44 and 47 patients, respectively. At 3 months, the change rate of serum zinc levels in the ZAH group was significantly higher than that in the PPZ group. Three months after the study, serum copper levels significantly decreased in the ZAH group, but not in the PPZ group. No significant differences were noted in anemia management in either group. ZAH was superior to PPZ in increasing serum zinc levels. Clinicians should note the stronger decline in serum copper levels when using ZAH for MHD patients.
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Affiliation(s)
- Teppei Okamoto
- Department of Urology, Oyokyo Kidney Research Institute Aomori Hospital, Aomori, Japan.,Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Shingo Hatakeyama
- Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Sakae Konishi
- Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Kazutaka Okita
- Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Yoshimi Tanaka
- Department of Urology, Oyokyo Kidney Research Institute Aomori Hospital, Aomori, Japan.,Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
| | - Kengo Imanishi
- Department of Urology, Oyokyo Kidney Research Institute Aomori Hospital, Aomori, Japan
| | - Tooru Takashima
- Department of Urology, Oyokyo Kidney Research Institute Aomori Hospital, Aomori, Japan
| | - Fumitada Saitoh
- Department of Urology, Oyokyo Kidney Research Institute Aomori Hospital, Aomori, Japan
| | - Tadashi Suzuki
- Department of Urology, Oyokyo Kidney Research Institute, Hirosaki, Japan
| | - Chikara Ohyama
- Department of Urology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
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Dalto DB, Audet I, Matte JJ. Impact of dietary zinc:copper ratio on the postprandial net portal appearance of these minerals in pigs1. J Anim Sci 2019; 97:3938-3946. [PMID: 31292635 DOI: 10.1093/jas/skz238] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2019] [Accepted: 07/09/2019] [Indexed: 12/16/2022] Open
Abstract
The present study compared the net intestinal absorption of zinc (Zn) and copper (Cu) after meals containing different dietary ratios among these trace elements. Ten 46-kg pigs were used in a cross-over design to assess the 10-h net portal-drained viscera (PDV) flux of serum Cu and Zn after ingestion of boluses containing ZnSO4 and CuSO4 in different Zn:Cu ratios (mg:mg): 120:20; 200:20; 120:8; and 200:8. Arterial Zn concentrations peaked within the first hour post-meal and responses were greater with 200 (0.9 to 1.8 mg/L) than with 120 mg (0.9 to 1.6 mg/L) of dietary Zn (dietary Zn × time, P = 0.05). Net PDV flux of Zn was greater (P = 0.02) with 200 than with 120 mg of dietary Zn and tended to be greater (P = 0.10) with 20 than with 8 mg of dietary Cu. The cumulative PDV appearance of Zn (% of dietary intake) was greater with 120 than 200 mg of dietary Zn from 8 h post-meal (P ≤ 0.04) and with 20 than 8 mg of dietary Cu from 7 h post-meal (P ≤ 0.05). At the end of the postprandial period (10 h), estimated PDV appearance of Zn was 16.0%, 18.4%, 12.0%, and 15.3% of Zn intake for 120:8, 120:20, 200:8, and 200:20 ratios, respectively. For Cu, irrespective of treatment, arterial values varied (P < 0.01) by less than 5% across postmeal times. Net PDV flux was not affected by treatments (P ≥ 0.12), but the value for ratio 120:20 was different from zero (P = 0.03). There was an interaction dietary Zn × dietary Cu on cumulative PDV appearance of Cu (% of dietary intake) at 30 min post-meal (P = 0.04) and thereafter at 3 h post-meal (P = 0.04). For the whole postprandial period (10 h), estimated PDV appearance of Cu was 61.9%, 42.1%, -17.1%, and 23.6% of Cu intake for 120:8, 120:20, 200:8, and 200:20 ratios, respectively. In conclusion, the present dietary amounts and ratios of Zn and Cu can affect the metabolic availability of both trace minerals for pigs. Ratios with 120 mg of dietary Zn maximized the postintestinal availability of both Zn and Cu.
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Affiliation(s)
- Danyel Bueno Dalto
- Sherbrooke Research and Development Centre, Agriculture and Agri-Food Canada, Sherbrooke, QC J1M 0C8, Canada
| | - Isabelle Audet
- Sherbrooke Research and Development Centre, Agriculture and Agri-Food Canada, Sherbrooke, QC J1M 0C8, Canada
| | - J Jacques Matte
- Sherbrooke Research and Development Centre, Agriculture and Agri-Food Canada, Sherbrooke, QC J1M 0C8, Canada
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Katayama K. Zinc and protein metabolism in chronic liver diseases. Nutr Res 2019; 74:1-9. [PMID: 31891865 DOI: 10.1016/j.nutres.2019.11.009] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2019] [Revised: 10/06/2019] [Accepted: 11/26/2019] [Indexed: 12/19/2022]
Abstract
The capacity to metabolize proteins is closely related to the hepatic functional reserve in patients with chronic liver disease, and hypoalbuminemia and hyperammonemia develop along with hepatic disease progression. Zinc deficiency, which is frequently observed in patients with chronic liver disease, significantly affects protein metabolism. Ornithine transcarbamylase is a zinc enzyme involved in the urea cycle. Its activity decreases because of zinc deficiency, thereby reducing hepatic capacity to metabolize ammonia. Because the glutamine-synthesizing system in skeletal muscles compensates for the decrease in ammonia metabolism, hyperammonemia does not develop in the early stages of chronic liver disease. However, branched-chain amino acids (BCAAs) are consumed with the increase in glutamine-synthesizing system reactions, leading to a decreased capacity to synthesize proteins, including albumin, due to amino acid imbalance. Upon further disease progression, skeletal muscle mass decreases because of nutritional deficiency, as well as the further decreased capacity to metabolize ammonia in the liver, whereby the capacity to detoxify ammonia reduces as a whole, resulting in hyperammonemia. BCAA supplementation therapy for nutritional deficiency in liver cirrhosis improves survival by correcting amino acid imbalance via recovery of the capacity to synthesize albumin, while zinc supplementation therapy improves the capacity to metabolize ammonia in the liver. Here, the efficacy of a combination of BCAA and zinc preparation for nutritional deficiency in liver cirrhosis, as well as its theoretical background, was reviewed.
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Affiliation(s)
- Kazuhiro Katayama
- Department of Hepato-Biliary and Pancreatic Oncology, Osaka, International Cancer Institute, Osaka, Japan.
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Chama M, Amadi BC, Chandwe K, Zyambo K, Besa E, Shaikh N, Ndao IM, Tarr PI, Storer C, Head R, Kelly P. Transcriptomic analysis of enteropathy in Zambian children with severe acute malnutrition. EBioMedicine 2019; 45:456-463. [PMID: 31229436 PMCID: PMC6642221 DOI: 10.1016/j.ebiom.2019.06.015] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2019] [Revised: 06/11/2019] [Accepted: 06/11/2019] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Children with severe acute malnutrition (SAM), with or without diarrhoea, often have enteropathy, but there are few molecular data to guide development of new therapies. We set out to determine whether SAM enteropathy is characterised by specific transcriptional changes which might improve understanding or help identify new treatments. METHODS We collected intestinal biopsies from children with SAM and persistent diarrhoea. mRNA was extracted from biopsies, sequenced, and subjected to a progressive set of complementary analytical approaches: NOIseq, Gene Set Enrichment Analysis (GSEA), and correlation analysis of phenotypic data with gene expression. FINDINGS Transcriptomic profiles were generated for biopsy sets from 27 children of both sexes, under 2 years of age, of whom one-third were HIV-infected. NOIseq analysis, constructed from phenotypic group extremes, revealed 66 differentially expressed genes (DEGs) out of 21,386 mapped to the reference genome. These DEGs include genes for mucins and mucus integrity, antimicrobial defence, nutrient absorption, C-X-C chemokines, proteases and anti-proteases. Phenotype - expression correlation analysis identified 1221 genes related to villus height, including increased cell cycling gene expression in more severe enteropathy. Amino acid transporters and ZIP zinc transporters were specifically increased in severe enteropathy, but transcripts for xenobiotic metabolising enzymes were reduced. INTERPRETATION Transcriptomic analysis of this rare collection of intestinal biopsies identified multiple novel elements of pathology, including specific alterations in nutrient transporters. Changes in xenobiotic metabolism in the gut may alter drug disposition. Both NOIseq and GSEA identified gene clusters similar to those differentially expressed in pediatric Crohn's disease but to a much lesser degree than those identified in coeliac disease. FUND: Bill & Melinda Gates Foundation OPP1066118. The funding agency had no role in study design, data collection, data analysis, interpretation, or writing of the report.
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Affiliation(s)
- Mubanga Chama
- Tropical Gastroenterology and Nutrition group, University of Zambia School of Medicine, Nationalist Road, Lusaka, Zambia
| | - Beatrice C Amadi
- Tropical Gastroenterology and Nutrition group, University of Zambia School of Medicine, Nationalist Road, Lusaka, Zambia
| | - Kanta Chandwe
- Tropical Gastroenterology and Nutrition group, University of Zambia School of Medicine, Nationalist Road, Lusaka, Zambia
| | - Kanekwa Zyambo
- Tropical Gastroenterology and Nutrition group, University of Zambia School of Medicine, Nationalist Road, Lusaka, Zambia
| | - Ellen Besa
- Tropical Gastroenterology and Nutrition group, University of Zambia School of Medicine, Nationalist Road, Lusaka, Zambia
| | - Nurmohammad Shaikh
- Department of Pediatrics, Washington University School of Medicine, St Louis, MO, United States
| | - I Malick Ndao
- Department of Pediatrics, Washington University School of Medicine, St Louis, MO, United States
| | - Philip I Tarr
- Department of Pediatrics, Washington University School of Medicine, St Louis, MO, United States
| | - Chad Storer
- Department of Genetics, Washington University School of Medicine, St Louis, MO, United States
| | - Richard Head
- Department of Genetics, Washington University School of Medicine, St Louis, MO, United States
| | - Paul Kelly
- Tropical Gastroenterology and Nutrition group, University of Zambia School of Medicine, Nationalist Road, Lusaka, Zambia; Blizard Institute, Barts & The London School of Medicine, Queen Mary University of London, 4 Newark Street, London, UK.
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Zinc induces iron uptake and DMT1 expression in Caco-2 cells via a PI3K/IRP2 dependent mechanism. Biochem J 2019; 476:1573-1583. [DOI: 10.1042/bcj20180939] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2018] [Revised: 03/29/2019] [Accepted: 05/15/2019] [Indexed: 11/17/2022]
Abstract
Abstract
The absorption of iron is influenced by numerous dietary and physiological factors. We have previously demonstrated that zinc treatment of intestinal cells increases iron absorption via induction of the apical membrane iron transporter divalent metal ion transporter-1 (DMT1). To better understand the mechanisms of zinc-induced iron absorption, we have studied the effect of zinc on iron uptake, iron transporter and iron regulatory protein (IRP 1 and 2) expression and the impact of the PI3K pathway in differentiated Caco-2 cells, an intestinal cell culture model. We found that zinc induces DMT1 protein and mRNA expression. Zinc-induced DMT1 expression and iron absorption were inhibited by siRNA silencing of DMT1. Furthermore, zinc treatment led to increased abundance of IRP2 protein in cell lysates and in polysomal fractions, implying its binding to target mRNAs. Zinc treatment induced Akt phosphorylation, indicating the activation of the PI3K pathway. LY294002, a specific inhibitor of PI3K inhibited zinc-induced Akt phosphorylation, iron uptake, DMT1 and IRP2 expression. Furthermore, LY294002 also decreased the basal level of DMT1 mRNA but not protein expression. siRNA silencing of IRP2 led to down-regulation of both basal and zinc-induced DMT1 protein expression, implying possible involvement of post-transcriptional regulatory mechanisms. In agreement with these findings, zinc treatment stabilized DMT1 mRNA levels in actinomycin D-treated cells. Based on these findings, we conclude that zinc-induced iron absorption involves elevation of DMT1 expression by stabilization of its mRNA, by a PI3K/IRP2-dependent mechanism.
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Li J, Gong C, Wang Z, Gao R, Ren J, Zhou X, Wang H, Xu H, Xiao F, Cao Y, Zhao Y. Oyster-Derived Zinc-Binding Peptide Modified by Plastein Reaction via Zinc Chelation Promotes the Intestinal Absorption of Zinc. Mar Drugs 2019; 17:md17060341. [PMID: 31181804 PMCID: PMC6627379 DOI: 10.3390/md17060341] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2019] [Revised: 06/03/2019] [Accepted: 06/05/2019] [Indexed: 02/06/2023] Open
Abstract
Zinc-binding peptides from oyster (Crassostrea gigas) have potential effects on zinc supplementation. The aim of this study was to prepare efficient zinc-binding peptides from oyster-modified hydrolysates by adding exogenous glutamate according to the plastein reaction and to further explore the zinc absorption mechanism of the peptide-zinc complex (MZ). The optimum conditions for the plastein reaction were as follows: pH 5.0, 40 °C, substrate concentration of 40%, pepsin dosage of 500 U/g, reaction time of 3 h and l-[1-13C]glutamate concentration of 10 mg/mL. The results of 13C isotope labelling suggested that the addition of l-[1-13C]glutamate contributed to the increase in the zinc-binding capacity of the peptide. The hydrophobic interaction was the main mechanism of action of the plastein reaction. Ultraviolet spectra and scanning electronic microscopy (SEM) revealed that the zinc-binding peptide could bind with zinc and form MZ. Furthermore, MZ could significantly enhance zinc bioavailability in the presence of phytic acid, compared to the commonly used ZnSO4. Additionally, MZ significantly promoted the intestinal absorption of zinc mainly through two pathways, the zinc ion channel and the small peptide transport pathway. Our work attempted to increase the understanding of the zinc absorption mechanism of MZ and to support the potential application of MZ as a supplementary medicine.
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Affiliation(s)
- Jianpeng Li
- College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China.
| | - Chen Gong
- College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China.
| | - Zaiyang Wang
- College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China.
| | - Ruichang Gao
- School of Food and Bioengineering, Jiangsu University, Zhenjiang 212013, China.
| | - Jiaoyan Ren
- School of Food Sciences and Engineering, South China University of Technology, Guangzhou 510641, China.
| | - Xiaodong Zhou
- Hisense (Shandong) Refrigerator Co., Ltd., Qingdao 266100, China.
| | - Haiyan Wang
- Hisense (Shandong) Refrigerator Co., Ltd., Qingdao 266100, China.
| | - He Xu
- Jiangsu Baoyuan Biotechnology Co., Ltd., Lianyungang 222100, China.
| | - Feng Xiao
- College of Food and Bioengineering, Henan University of Science and Technology, Luoyang 471023, China.
| | - Yuhui Cao
- College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China.
| | - Yuanhui Zhao
- College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China.
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41
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Bauer BU, Rapp C, Mülling CKW, Meissner J, Vogel C, Humann-Ziehank E. Influence of dietary zinc on the claw and interdigital skin of sheep. J Trace Elem Med Biol 2018; 50:368-376. [PMID: 30262307 DOI: 10.1016/j.jtemb.2018.07.026] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2018] [Revised: 07/26/2018] [Accepted: 07/27/2018] [Indexed: 01/24/2023]
Abstract
Claw diseases like interdigital dermatitis and footrot threaten sheep health and are major welfare issues. Several studies mainly done in cattle suggested that zinc (Zn) supplementation may improve claw integrity. However, Zn supplements may differ markedly regarding Zn bioavailability. Zn bound to single amino acids has been shown to be more bioavailable than inorganic Zn sources. The aim of this study was to determine the effect of different Zn supplements on the integrity of the claw and interdigital skin of healthy sheep. At weaning 30 Merino lambs were randomly allocated to three different dietary treatments which were provided through the pelleted concentrates as follows: 1) no supplemental Zn (Zn0); 2) addition of 40 mg/kg Zn as Zn sulphate (ZnS); 3) addition of 40 mg/kg organic Zn as Zn amino acid complex (CZn). Barley straw and pelleted concentrates were given ad-libitum. The calculated Zn concentration of the total diet (roughage and concentrate) without supplemental Zn (Zn0) was 38 mg Zn/kg DM. The concentrates were formulated to meet the nutritional requirements for growing lambs and contained 207 g/kg DM crude protein and 12.4 MJ/kg DM metabolizable energy. After 8 weeks the lambs were slaughtered and the following specimens were collected: blood serum, liver, sole and coronary band of the claw, and interdigital skin. Serum and tissue Zn and copper (Cu) concentrations and claw hardness were determined. Routine pathohistology and electron microscopy were conducted. Franz diffusion cell system and Ki-67 immunostaining were used to determine the permeability of the interdigital skin and the keratinocyte proliferation in the basal layer of sole horn, coronary band and interdigital skin, respectively. The concentrations of Zn and Cu in serum and liver tissue as well as the Zn concentration in claw horn were not affected by dietary treatment. Zn0 lambs showed higher (p < 0.05) Cu concentrations in claw horn compared to both Zn supplemented groups. Routine pathohistology as well as electron microscopy did not show significant morphological differences between the three groups. Franz diffusion cell system proved to be a suitable method examining the interdigital skin permeability, but the group differences in this study were not significant. Dietary treatment did not affect keratinocyte proliferation in the coronary band. In the sole keratinocyte proliferation was significantly higher (p < 0.05) in the Zn0 group compared to CZn with ZnS being intermediate. Keratinocyte proliferation in the interdigital skin was significantly higher (p < 0.05) in the CZn group compared to the Zn0 with ZnS being intermediate. The results of the current experiment indicate that serum and tissue Zn concentrations and horn hardness are not affected by adding a moderate amount of Zn sulphate or Zn amino acid complex to a basal diet. However, supplemental Zn amino acid complex seems to affect keratinocyte proliferation of interdigital skin and sole horn of lambs. Effects on skin permeability should be retested using a higher number of animals prospectively.
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Affiliation(s)
- Benjamin U Bauer
- Tiergesundheitsdienst Bayern e. V., Senator-Gerauer-Str. 23, 85586, Poing, Germany.
| | - Christof Rapp
- Zinpro Animal Nutrition Inc., Akkerdistel 2 E, 5831 PJ Boxmeer, The Netherlands.
| | - Christoph K W Mülling
- Universität Leipzig, Veterinär-Anatomisches Institut, An den Tierkliniken 43, 04103, Leipzig, Germany.
| | - Jessica Meissner
- Stiftung Tierärztliche Hochschule Hannover, Institut für Pharmakologie, Toxikologie und Pharmazie, Bünteweg 17, 30559, Hannover, Germany.
| | - Charlotte Vogel
- Stiftung Tierärztliche Hochschule Hannover, Institut für Biometrie, Epidemiologie und Informationsverarbeitung, Bünteweg 2, 30559, Hannover, Germany.
| | - Esther Humann-Ziehank
- Stiftung Tierärztliche Hochschule Hannover, Klinik für kleine Klauentiere und forensische Medizin und Ambulatorische Klinik, Bischofsholer Damm 15, 30173, Hannover, Germany.
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42
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Nishito Y, Kambe T. Absorption Mechanisms of Iron, Copper, and Zinc: An Overview. J Nutr Sci Vitaminol (Tokyo) 2018; 64:1-7. [PMID: 29491267 DOI: 10.3177/jnsv.64.1] [Citation(s) in RCA: 90] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
Essential trace elements play pivotal roles in numerous structural and catalytic functions of proteins. Adequate intake of essential trace elements from the daily diet is indispensable to the maintenance of health, and their deficiency leads to a variety of conditions. However, excessive amounts of these trace elements may be highly toxic, and in some cases, may cause damage by the production of harmful reactive oxygen species. Homeostatic dysregulation of their metabolism increases the risk of developing diseases. Specific transport proteins that facilitate influx or efflux of trace elements play key roles in maintaining the homeostasis. Recent elucidation of their crucial functions significantly facilitated our understanding of the molecular mechanisms of iron (Fe), copper (Cu), and zinc (Zn) absorption in the small intestine. This paper summarizes their absorption mechanisms, with a focus on indispensable functions of the molecules involved in it, and briefly discusses the mechanisms of homeostatic control of each element at the cellular and systemic levels.
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Affiliation(s)
- Yukina Nishito
- The Division of Integrated Life Science, Graduate School of Biostudies, Kyoto University
| | - Taiho Kambe
- The Division of Integrated Life Science, Graduate School of Biostudies, Kyoto University
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Maares M, Keil C, Koza J, Straubing S, Schwerdtle T, Haase H. In Vitro Studies on Zinc Binding and Buffering by Intestinal Mucins. Int J Mol Sci 2018; 19:E2662. [PMID: 30205533 PMCID: PMC6164875 DOI: 10.3390/ijms19092662] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2018] [Revised: 09/03/2018] [Accepted: 09/06/2018] [Indexed: 12/15/2022] Open
Abstract
The investigation of luminal factors influencing zinc availability and accessibility in the intestine is of great interest when analyzing parameters regulating intestinal zinc resorption. Of note, intestinal mucins were suggested to play a beneficial role in the luminal availability of zinc. Their exact zinc binding properties, however, remain unknown and the impact of these glycoproteins on human intestinal zinc resorption has not been investigated in detail. Thus, the aim of this study is to elucidate the impact of intestinal mucins on luminal uptake of zinc into enterocytes and its transfer into the blood. In the present study, in vitro zinc binding properties of mucins were analyzed using commercially available porcine mucins and secreted mucins of the goblet cell line HT-29-MTX. The molecular zinc binding capacity and average zinc binding affinity of these glycoproteins demonstrates that mucins contain multiple zinc-binding sites with biologically relevant affinity within one mucin molecule. Zinc uptake into the enterocyte cell line Caco-2 was impaired by zinc-depleted mucins. Yet this does not represent their form in the intestinal lumen in vivo under zinc adequate conditions. In fact, zinc-uptake studies into enterocytes in the presence of mucins with differing degree of zinc saturation revealed zinc buffering by these glycoproteins, indicating that mucin-bound zinc is still available for the cells. Finally, the impact of mucins on zinc resorption using three-dimensional cultures was studied comparing the zinc transfer of a Caco-2/HT-29-MTX co-culture and conventional Caco-2 monoculture. Here, the mucin secreting co-cultures yielded higher fractional zinc resorption and elevated zinc transport rates, suggesting that intestinal mucins facilitate the zinc uptake into enterocytes and act as a zinc delivery system for the intestinal epithelium.
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Affiliation(s)
- Maria Maares
- Department of Food Chemistry and Toxicology, Berlin Institute of Technology, Gustav-Meyer-Allee 25, D-13355 Berlin, Germany.
| | - Claudia Keil
- Department of Food Chemistry and Toxicology, Berlin Institute of Technology, Gustav-Meyer-Allee 25, D-13355 Berlin, Germany.
| | - Jenny Koza
- Department of Food Chemistry and Toxicology, Berlin Institute of Technology, Gustav-Meyer-Allee 25, D-13355 Berlin, Germany.
| | - Sophia Straubing
- Department of Food Chemistry and Toxicology, Berlin Institute of Technology, Gustav-Meyer-Allee 25, D-13355 Berlin, Germany.
| | - Tanja Schwerdtle
- Institute of Nutritional Science, University of Potsdam, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany.
- TraceAge-DFG Research Unit on Interactions of essential trace elements in healthy and diseased elderly, Potsdam-Berlin-Jena, Germany.
| | - Hajo Haase
- Department of Food Chemistry and Toxicology, Berlin Institute of Technology, Gustav-Meyer-Allee 25, D-13355 Berlin, Germany.
- TraceAge-DFG Research Unit on Interactions of essential trace elements in healthy and diseased elderly, Potsdam-Berlin-Jena, Germany.
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44
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Goff JP. Invited review: Mineral absorption mechanisms, mineral interactions that affect acid-base and antioxidant status, and diet considerations to improve mineral status. J Dairy Sci 2018; 101:2763-2813. [PMID: 29397180 DOI: 10.3168/jds.2017-13112] [Citation(s) in RCA: 181] [Impact Index Per Article: 25.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2017] [Accepted: 12/06/2017] [Indexed: 12/18/2022]
Abstract
Several minerals are required for life to exist. In animals, 7 elements (Ca, P, Mg, Na, K, Cl, and S) are required to be present in the diet in fairly large amounts (grams to tens of grams each day for the dairy cow) and are termed macrominerals. Several other elements are termed microminerals or trace minerals because they are required in much smaller amounts (milligrams to micrograms each day). In most cases the mineral in the diet must be absorbed across the gastrointestinal mucosa and enter the blood if it is to be of value to the animal. The bulk of this review discusses the paracellular and transcellular mechanisms used by the gastrointestinal tract to absorb each of the various minerals needed. Unfortunately, particularly in ruminants, interactions between minerals and other substances within the diet can occur within the digestive tract that impair mineral absorption. The attributes of organic or chelated minerals that might permit diet minerals to circumvent factors that inhibit absorption of more traditional inorganic forms of these minerals are discussed. Once absorbed, minerals are used in many ways. One focus of this review is the effect macrominerals have on the acid-base status of the animal. Manipulation of dietary cation and anion content is commonly used as a tool in the dry period and during lactation to improve performance. A section on how the strong ion theory can be used to understand these effects is included. Many microminerals play a role in the body as cofactors of enzymes involved in controlling free radicals within the body and are vital to antioxidant capabilities. Those same minerals, when consumed in excess, can become pro-oxidants in the body, generating destructive free radicals. Complex interactions between minerals can compromise the effectiveness of a diet in promoting health and productivity of the cow. The objective of this review is to provide insight into some of these mechanisms.
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Affiliation(s)
- Jesse P Goff
- Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames 50011.
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Mechanistic insights into the protective impact of zinc on sepsis. Cytokine Growth Factor Rev 2017; 39:92-101. [PMID: 29279185 DOI: 10.1016/j.cytogfr.2017.12.002] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2017] [Accepted: 12/19/2017] [Indexed: 12/11/2022]
Abstract
Sepsis, a systemic inflammation as a response to a bacterial infection, is a huge unmet medical need. Data accumulated over the last decade suggest that the nutritional status of patients as well as composition of their gut microbiome, are strongly linked with the risk to develop sepsis, the severity of the disease and prognosis. In particular, the essential micronutrient zinc is essential in the resistance against sepsis and has shown to be protective in animal models as well as in human patients. The potential mechanisms by which zinc protects in sepsis are discussed in this review paper: we will focus on the inflammatory response, chemotaxis, phagocytosis, immune response, oxidative stress and modulation of the microbiome. A full understanding of the mechanism of action of zinc may open new preventive and therapeutic interventions in sepsis.
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Matte JJ, Girard CL, Guay F. Intestinal fate of dietary zinc and copper: Postprandial net fluxes of these trace elements in portal vein of pigs. J Trace Elem Med Biol 2017; 44:65-70. [PMID: 28965602 DOI: 10.1016/j.jtemb.2017.06.003] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2017] [Revised: 06/02/2017] [Accepted: 06/06/2017] [Indexed: 01/20/2023]
Abstract
In pig, the assessment of bioavailability of dietary trace minerals with classical approaches such as relative bioavailability estimates or digestive tract balances have often generated inconsistent responses. In the present study, net portal-drained-viscera fluxes were monitored after a meal to assess intestinal absorption of zinc (Zn) or copper (Cu) according to dietary sources and levels of these trace minerals. Twelve pigs were surgically equipped with portal and carotid catheters and a portal ultrasonic flow probe for 12-h postprandial measurements. In a cross-over design, pigs received boluses of inorganic (I) or organic (O) dietary Cu and Zn at adequate (A, 20 and 200mg, respectively) or high (H, 40 and 400mg, respectively) level just before a 0.8-kg meal (semi-purified diet). Whatever treatments, arterial Zn increased by 72% at 45min postprandial and gradually declined thereafter (P<0.01). Arterial Zn were greater by 11% after O than I (P=0.02) and by 19% after H than A (P<0.01) meals. Net portal-drained-viscera fluxes of Zn during the first 240min postprandial were greater by 44% after O than I (P=0.10) and by 51% after H than A (P=0.07) meals. For Cu, portal-drained-viscera fluxes of Cu up to 240min postprandial were greater (P=0.03) after A than H meals. Those results suggest that Zn is absorbed rapidly, likely in the upper digestive tract of pigs and, whatever dietary levels, more efficiently after O meals. It appears that H levels of both Zn and Cu interfered with intestinal absorption of Cu and/or stimulate post-absorption enterocyte sequestration of this mineral.
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Affiliation(s)
- J Jacques Matte
- Sherbrooke Research and Development Centre, Agriculture and Agri-Food Canada, Sherbrooke, Quebec J1M 0C8, Canada.
| | - Christiane L Girard
- Sherbrooke Research and Development Centre, Agriculture and Agri-Food Canada, Sherbrooke, Quebec J1M 0C8, Canada.
| | - Frédéric Guay
- Département des Sciences animales, Université Laval, Pavillon Paul-Comtois 2425, rue de l'Agriculture, Québec, QC, G1V 0A6, Canada.
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Zinc Signals and Immunity. Int J Mol Sci 2017; 18:ijms18102222. [PMID: 29064429 PMCID: PMC5666901 DOI: 10.3390/ijms18102222] [Citation(s) in RCA: 169] [Impact Index Per Article: 21.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2017] [Revised: 10/13/2017] [Accepted: 10/19/2017] [Indexed: 01/11/2023] Open
Abstract
Zinc homeostasis is crucial for an adequate function of the immune system. Zinc deficiency as well as zinc excess result in severe disturbances in immune cell numbers and activities, which can result in increased susceptibility to infections and development of especially inflammatory diseases. This review focuses on the role of zinc in regulating intracellular signaling pathways in innate as well as adaptive immune cells. Main underlying molecular mechanisms and targets affected by altered zinc homeostasis, including kinases, caspases, phosphatases, and phosphodiesterases, will be highlighted in this article. In addition, the interplay of zinc homeostasis and the redox metabolism in affecting intracellular signaling will be emphasized. Key signaling pathways will be described in detail for the different cell types of the immune system. In this, effects of fast zinc flux, taking place within a few seconds to minutes will be distinguish from slower types of zinc signals, also designated as “zinc waves”, and late homeostatic zinc signals regarding prolonged changes in intracellular zinc.
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Abstract
Cynk jest jednym z głównych pierwiastków śladowych organizmu, spełniającym rolę katalityczną, strukturalną i regulacyjną. Jest niezbędny do podziałów komórkowych i różnicowania powstających komórek, uczestniczy w homeostazie, reakcjach odpornościowych, w apoptozie i starzeniu się organizmu. Cynk jest również składnikiem wielu enzymów i białek oraz odgrywa ważną rolę w spermatogenezie i syntezie hormonów steroidowych. Niedostateczna podaż cynku dotyczy ok. 30% ludności świata. Oprócz niedostatecznej podaży z pokarmem, przyczyną niedoboru cynku mogą być niektóre schorzenia oraz nieprawidłowe wchłanianie tego pierwiastka. Schorzenia, wynikające z niedoboru tego pierwiastka, mogą występować zarówno u dzieci, jak i dorosłych. Suplementacja diety preparatami cynku w wielu przypadkach jest niezbędna, jednak samodzielne jego stosowanie, bez stwierdzonego niedoboru i bez konsultacji z lekarzem, może doprowadzić do występowania działań niepożądanych w wyniku jego nadużywania, w tym także niebezpiecznych interakcji z innymi stosowanymi preparatami i żywnością.
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Knez M, Graham RD, Welch RM, Stangoulis JCR. New perspectives on the regulation of iron absorption via cellular zinc concentrations in humans. Crit Rev Food Sci Nutr 2017; 57:2128-2143. [PMID: 26177050 DOI: 10.1080/10408398.2015.1050483] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Iron deficiency is the most prevalent nutritional deficiency, affecting more than 30% of the total world's population. It is a major public health problem in many countries around the world. Over the years various methods have been used with an effort to try and control iron-deficiency anemia. However, there has only been a marginal reduction in the global prevalence of anemia. Why is this so? Iron and zinc are essential trace elements for humans. These metals influence the transport and absorption of one another across the enterocytes and hepatocytes, due to similar ionic properties. This paper describes the structure and roles of major iron and zinc transport proteins, clarifies iron-zinc interactions at these sites, and provides a model for the mechanism of these interactions both at the local and systemic level. This review provides evidence that much of the massive extent of iron deficiency anemia in the world may be due to an underlying deficiency of zinc. It explains the reasons for predominance of cellular zinc status in determination of iron/zinc interactions and for the first time thoroughly explains mechanisms by which zinc brings about these changes.
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Affiliation(s)
- Marija Knez
- a School of Biological Sciences, Flinders University , Adelaide , South Australia , Australia
| | - Robin D Graham
- a School of Biological Sciences, Flinders University , Adelaide , South Australia , Australia
| | - Ross M Welch
- b USDA/ARS, Robert W. Holley Centre for Agriculture and Health, Cornell University , Ithaca , New York , USA
| | - James C R Stangoulis
- a School of Biological Sciences, Flinders University , Adelaide , South Australia , Australia
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Characterization of zinc amino acid complexes for zinc delivery in vitro using Caco-2 cells and enterocytes from hiPSC. Biometals 2017; 30:643-661. [PMID: 28717982 PMCID: PMC5646115 DOI: 10.1007/s10534-017-0033-y] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2017] [Accepted: 07/06/2017] [Indexed: 02/07/2023]
Abstract
Zn is essential for growth and development. The bioavailability of Zn is affected by several factors such as other food components. It is therefore of interest, to understand uptake mechanisms of Zn delivering compounds to identify ways to bypass the inhibitory effects of these factors. Here, we studied the effect of Zn amino acid conjugates (ZnAAs) on the bioavailabilty of Zn. We used Caco-2 cells and enterocytes differentiated from human induced pluripotent stem cells from a control and Acrodermatitis enteropathica (AE) patient, and performed fluorescence based assays, protein biochemistry and atomic absorption spectrometry to characterize cellular uptake and absorption of ZnAAs. The results show that ZnAAs are taken up by AA transporters, leading to an intracellular enrichment of Zn mostly uninhibited by Zn uptake antagonists. Enterocytes from AE patients were unable to gain significant Zn through exposure to ZnCl2 but did not show differences with respect to ZnAAs. We conclude that ZnAAs may possess an advantage over classical Zn supplements such as Zn salts, as they may be able to increase bioavailability of Zn, and may be more efficient in patients with AE.
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