ArticleLiterature Review

Zinc-Altered Immune Function and Cytokine Production

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Abstract

Although the intriguing role of zinc as an essential trace element for immune function is well established, particular progress in determining the molecular principles of action of this ion was made recently. Leukocyte responsiveness is delicately regulated by zinc concentration. Zinc deficiency as well as supraphysiologic levels impair immune function. Furthermore, the activities of many immunostimulants frequently used in immunologic studies are influenced by zinc concentration. Therefore, our knowledge from in vitro studies is widely dependent on the zinc concentration, and when not in physiologic range, immunologic responses are artificially low. Decreased production of TH1 cytokines and interferon-alpha by leukocytes in the healthy elderly person is correlated with low zinc serum level. The defect in interferon-alpha production is reconstituted by the addition of physiologic amounts of zinc in vitro. Interestingly, zinc induces cytokine production by isolated leukocytes. Zinc induces monocytes to produce interleukin-1, interleukin-6 and tumor necrosis factor-alpha in peripheral blood mononuclear cells and separated monocytes. This effect is higher in serum-free medium. However, only in the presence of serum does zinc also induce T cells to produce lymphokines. This effect on T cells is mediated by cytokines produced by monocytes. Stimulation also requires cell-to-cell contact of monocytes and T cells. Information is presented to illustrate the concepts that the zinc concentration must be taken into account whenever in vitro studies are made or complex alterations of immune functions are observed in vivo.

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... Vitamins A, C, D, E, B6, B12, and folate, and the trace elements Zn, Fe, Cu, Se, as well as the mineral Mg comprise a group of nutrients that support the entire continuum of virus-host immune responses. Their contributions range from the regulation of number and function of innate immune cells such as neutrophils, natural killer cells, monocytes, and macrophages [36,37,45,54,[61][62][63][64][65][66][67][68][69][70][71][72][73], the production of pro-, and anti-inflammatory cytokines, the responses to inflammation, the oxidative burst function, the reductive-oxidative hemodynamics [36,37,45,[61][62][63][64]71,72,[74][75][76][77][78][79][80][81][82][83][84][85], to the responses of adaptive immunity, including differentiation, proliferation, and functions of T-cells [32,36,37,45,54,71,77,84,[86][87][88][89][90][91][92][93][94][95], the interactions with the presenting viral antigens [37,54,71,73,96], and the production and development of virus-specific antibodies [36,37,45,71,73,97,98]. ...
... Vitamin E also increases the proportion of antigen-experienced memory T-cells [96]. • involves in antibody production, mainly the immunoglobulin G [37,97,98]. Selenium • component of selenoproteins that are essential for the functions of the immune system and the reductive-oxidative homeostasis [61,148] • modulates the activities of virus-induced innate and adaptive immunity through the regulation of IFN α, IFN γ, and IFN β production • influences on the functions and differentiation of natural killer cells and T-cells, and the antibody production [36,45,71,84,95,149,150]. ...
... It supports the proliferation of cytotoxic T cells, the differentiation, development, and activation of T-cells, the cytokine production of Th1 cells, and the development of regulatory T cells [36,54,77,[92][93][94]. Zinc is involved in antibody production, mainly the immunoglobulin G antibody [37,97,98]. ...
Article
COVID-19 rapidly turned to a global pandemic posing lethal threats to overwhelming health care capabilities, despite its relatively low mortality rate. The clinical respiratory symptoms include dry cough, fever, anosmia, breathing difficulties, and subsequent respiratory failure. No known cure is available for COVID-19. Apart from the anti-viral strategy, the supports of immune effectors and modulation of immunosuppressive mechanisms is the rationale immunomodulation approach in COVID-19 management. Diet and nutrition are essential for healthy immunity. However, a group of micronutrients plays a dominant role in immunomodulation. The deficiency of most nutrients increases the individual susceptibility to virus infection with a tendency for severe clinical presentation. Despite a shred of evidence, the supplementation of a single nutrient is not promising in the general population. Individuals at high-risk for specific nutrient deficiencies likely benefit from supplementation. The individual dietary and nutritional status assessments are critical for determining the comprehensive actions in COVID-19.
... It has been shown that high concentrations of zinc have a negative effect on the functioning of leukocytes [190], and that levels of zinc greater than 30 mM have more inhibitory than positive effects on the components of the immune system, according to in vitro studies. However, such inhibitory activity, conferred by high zinc concentrations can be used in appropriately targeted pharmacotherapy. ...
... In the brains of patients suffering from Alzheimer's disease all three metals, redox active copper and iron and redox inactive zinc are significantly elevated, in comparison with surrounding healthy tissues [194]. A protective role for zinc can be explained by its competition with copper (or iron) to interact with Aβ, since the coordination of zinc to Aβ changes its conformation and prevents it from interacting with copper, thus circumventing the formation of hydroxyl radicals via the Fenton reaction that is otherwise catalyzed by the Cu-Aβ complex [190]. ...
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In total, twenty elements appear to be essential for the correct functioning of the human body, half of which are metals and half are non-metals. Among those metals that are currently considered to be essential for normal biological functioning are four main group elements, sodium (Na), potassium (K), magnesium (Mg), and calcium (Ca), and six d-block transition metal elements, manganese (Mn), iron (Fe), cobalt (Co), copper (Cu), zinc (Zn) and molybdenum (Mo). Cells have developed various metallo-regulatory mechanisms for maintaining a necessary homeostasis of metal-ions for diverse cellular processes, most importantly in the central nervous system. Since redox active transition metals (for example Fe and Cu) may participate in electron transfer reactions, their homeostasis must be carefully controlled. The catalytic behaviour of redox metals which have escaped control, e.g. via the Fenton reaction, results in the formation of reactive hydroxyl radicals, which may cause damage to DNA, proteins and membranes. Transition metals are integral parts of the active centres of numerous enzymes (e.Dg. Cu,Zn-SOD, Mn-SOD, Catalase) which catalyze chemical reactions at physiologically compatible rates. Either a deficiency, or an excess of essential metals may result in various disease states arising in an organism. Some typical ailments that are characterized by a disturbed homeostasis of redox active metals include neurological disorders (Alzheimer's, Parkinson's and Huntington's disorders), mental health problems, cardiovascular diseases, cancer, and diabetes. To comprehend more deeply the mechanisms by which essential metals, acting either alone or in combination, and/or through their interaction with non-essential metals (e.g. chromium) function in biological systems will require the application of a broader, more interdisciplinary approach than has mainly been used so far. It is clear that a stronger cooperation between bioinorganic chemists and biophysicists - who have already achieved great success in understanding the structure and role of metalloenzymes in living systems - with biologists, will access new avenues of research in the systems biology of metal ions. With this in mind, the present paper reviews selected chemical and biological aspects of metal ions and their possible interactions in living systems under normal and pathological conditions.
... Operating as such, Zn fingers recognize certain DNA sequences and thus ensure binding of specific regulatory proteins with them. Zinc is also a component of the aminoacyl-tRNA-synthetases and ЕF-1 translation factor (Dardenne and Jean-Marie, 1994;Rink and Kirchner, 2000;Rish, 2003). ...
... The necessity of Zn for the immune system has been known for decades. Zinc deficiency is often associated with an immunodeficiency disorder (Rink and Kirchner, 2000). It is conventional to distinguish between Zn effects on the cell cycle and proliferation and the specific influence of this element on cells of the immune system (Dardenne and Jean-Marie, 1994). ...
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Abstract—The review presents summarized information on a new research avenue in biogeochemistry and geochemical ecology: relationships between the microcosm (viruses) and manifestations of animal and human pathologies. Some aspects of the biological action of selenium, zinc, copper and iodine, their influence on the manifestation and course of viral infections are considered. Attention is focused on the antioxidant, membrane-protective, boosting immunity, hormonal functions of trace elements, and on the antibacterial and antiviral properties of metallic copper and its compounds. The criteria currently applied in assessing the Se status of territories are compared with the incidence of COVID-19 and HIV in the population of the Russian Federation. In some cases, selenium deficiency in the environment is shown to be associated with a higher susceptibility to RNA viral infections. Emphasis is put on the necessity of improving the criteria for assessing the trace element status of territories and further studies in the geochemical ecology of viruses and their role in the biosphere. Keywords: biological role, viral infections, geochemical ecology, iodine, copper, selenium, COVID-19 DOI: 10.1134/S0016702922020045
... cytokine response to antigenic/mitogenic stimulation [11,12]. In turn, ZD is causative of decreasing the ability of T cells to produce adequate levels of cytokines in response to stimulation [13,14]. While some proinflammatory cytokines, such as interleukin 6 (IL-6) are released in greater amounts (inflammaging), the production of other cytokines such as IL-2 decreases sharply in old age as well as in ZD [15][16][17]. ...
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Background Aging is accompanied by a dramatic decline in the interleukin (IL)-2 production capacity of human immune cells, thus making seniors more susceptible to a variety of age-related diseases. A common cause of impaired cytokine production in advanced age is a deficiency of the essential micronutrient zinc. Nevertheless, the molecular mechanisms underlying a zinc deficiency-induced decrease in IL-2 production have not yet been satisfactorily elucidated. Recent animal and in vitro data suggested that the transcription factor cAMP-responsive element modulator (CREM) $$\alpha$$ α plays a critical role in T cells´ disturbed IL-2 production in suboptimal zinc conditions. However, its role in the human aging process and the possibility of influencing this detrimental process by short-term zinc supplementation have not yet been evaluated. Results Comparing peripheral lymphocytes of 23 young and 31 elderly subjects with either high, intermediate, or deficient zinc status, we observed zinc-dependent regulation of the IL-2 production mediated by the transcription factor CREM $$\alpha$$ α . For the first time in humans, we report a mutual relationship between low zinc levels, high CREM $$\alpha$$ α expression, subsequent impaired IL-2 production, and vice versa. Remarkably, an average of only 6 days of in vivo zinc supplementation to zinc-deficient seniors was sufficient to rapidly improve zinc status, reverse CREM $$\alpha$$ α overexpression, and counteract subsequent low IL-2 production rates. Conclusions Our ex vivo and in vivo data identify zinc deficiency-mediated CREM $$\alpha$$ α overexpression as a key cellular mechanism underlying impaired IL-2 production in the elderly and point toward the use of zinc as a rapidly immune-enhancing add-on nutraceutical in geriatric therapy. Graphical abstract During the aging process, there is a progressive decrease in zinc status, which in turn leads to overexpression of the transcription factor CREM $$\mathrm{\alpha }$$ α in peripheral lymphocytes. CREMα is a negative regulator of the IL-2 gene, the overexpression of which dramatically limits adequate IL-2 production. This deleterious mechanism can be counteracted by short-term oral zinc administration, which can adjust IL-2 production in old, zinc-deficient individuals to a level similar to that of young adults.
... p < 0.01) with Ca content in colostrum. Zn plays an important role in enzyme systems, protein synthesis, and many other biochemical reactions (26). Even though the treatment did not shift the Zn concentration in colostrum or commercial milk, the HN3 significantly increased the overall Zn concentration. ...
Article
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Transition dairy cows experience sudden changes in both metabolic and immune functions, which lead to many diseases in postpartum cows. Therefore, it is crucial to monitor and guarantee the nutritional and healthy status of transition cows. The objective of this study was to determine the effect of diet enriched in n-3 or n-6 polyunsaturated fatty acid (PUFA) on colostrum composition and blood immune index of multiparous Holstein cows and neonatal calves during the transition period. Forty-five multiparous Holstein dairy cows at 240 days of pregnancy were randomly assigned to receive 1 of 3 isoenergetic and isoprotein diets: 1) CON, hydrogenated fatty acid (control), 1% of hydrogenated fatty acid [diet dry matter (DM) basis] during prepartum and postpartum, respectively; 2) HN3, 3.5% of extruding flaxseed (diet DM basis, n-3 PUFA source); 3) HN6, 8% of extruding soybeans (diet DM basis, C18:2n-6 PUFA source). Diets containing n-3 and n-6 PUFA sources decreased colostrum immunoglobulin G (IgG) concentration but did not significantly change the colostrum IgG yield compared with those with CON. The commercial milk yield (from 14 to 28 days after calving) was higher in the HN3 and HN6 than that in the CON. Furthermore, the n-3 PUFA source increased neutrophil cell counts in blood during the prepartum period and increased neutrophil percentage during the postpartum period when compared with those with control treatment. Diets containing supplemental n-3 PUFA decreased the serum concentration of interleukin (IL)-1β in maternal cows compared with those in control and n-6 PUFA during prepartum and postpartum. In addition, the neonatal calf serum concentration of tumor necrosis factor (TNF) was decreased in HN3 compared with that in the HN6 treatment. The diet with the n-3 PUFA source could potentially increase the capacity of neutrophils to defend against pathogens in maternal cows by increasing the neutrophil numbers and percentage during the transition period. Meanwhile, the diet with n-3 PUFA source could decrease the pro-inflammatary cytokine IL-1β of maternal cows during the transition period and decline the content of pro-inflammatary cytokine TNF of neonatal calves. It suggested that the highest milk production in n-3 PUFA treatment may partially be due to these beneficial alterations.
... Similarly, BTE has a strong positive correlation with PRO. The standardized path coefficient was 0.25, which was statistically significant, indicating that trace elements could affect the immunoglobulin as effectively as previous research evidences (22)(23)(24)(25)(26). The canonical coefficients is statistically significant, indicating that the role of most elements is the same as the previous results (27)(28)(29). ...
Article
Background: To study the association between indoor environment (MiE), blood trace elements (BTE), and immune globulin (PRO) among workers from vegetables plastic greenhouse, and to assess the mediate effects on MiE and PRO by BTE. Methods: Overall, 168 practitioner and corresponding sheds were included from cross-sectional study in 2016. BTE and PRO were determined by physical test and MiE data from field and laboratory measurement. The association was assessed using canonical correlation analysis. The direct and indirect effects between MiE, PRO and BTE were conducted by structural equation model. 5000 times bootstrap methods were performed to estimate coefficient and 95% confidence interval. Results: MiE was moderately correlated with BTE (canonical coefficient = 0.439), and BTE was strongly correlated with PRO (canonical coefficient = 0.514 and 0.481). No statistical evidence was found for the overall impact of MiE on PRO, and BTE as an intermediary affecting its relevance was not confirmed. Only the path way of the BTE impact on PRO had a significant positive effect (P=0.012). Conclusion: BTE was positively associated with PRO, therefore, reducing exposure in greenhouse is a pathway to remain blood trace elements, and further effect the immune protein in human body.
... Zinc is required for both the innate and adaptive immune systems. Zinc deficiency induces a cumulative loss of B cell and T cell maturation, which subsequently results in lymphopenia and impaired natural killer (NK) cell function (10,21). It has been proposed that zinc administration could restore lymphocyte production and NK cell activity (22). ...
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Background Zinc is an essential trace element involved in multiple metabolic processes. Acute kidney injury (AKI) is associated with low plasma zinc, but outcomes with zinc supplementation in critically ill patients with AKI remain unknown. Our objective was to investigate the effectiveness of zinc supplementation in this patient population. Methods Critically ill patients with AKI were identified from the Medical Informative Mart for Intensive Care IV database. Prosperity score matching (PSM) was applied to match patients receiving zinc treatment to those without zinc treatment. The association between zinc sulfate use and in-hospital mortality and 30-day mortality, need for renal replacement therapy (RRT), and length of stay was determined by logistic regression and Cox proportional hazards modeling. Results A total of 9,811 AKI patients were included in the study. PSM yielded 222 pairs of patients who received zinc treatment and those who did not. Zinc supplementation was associated with reduced in-hospital mortality (HR = 0.48 (95% CI: 0.28, 0.83) P = 0.009) and 30-day mortality (HR = 0.51 (95% CI, 0.30, 0.86) P = 0.012). In the subgroup analysis, zinc use was associated with reduced in-hospital mortality in patients with stage 1 AKI and those with sepsis. Conclusions Zinc supplementation was associated with improved survival in critically ill patients with AKI. The supplementation was especially effective in those with stage 1 AKI and sepsis. These results need to be verified in randomized controlled trials.
... The cells are sustained mainly by granulocytes and macrophages, specifically entrap pathogens, including viruses and bacteria. 47,48 There is a decrease in the synthesis of antibodies when Zn is depleted. The innate immune system is also affected by a decline in the activity of natural killer cells in this condition. ...
Article
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Due to the absence of successful therapy, vaccines for protection are continuously being developed. Since vaccines must be thoroughly tested, viral respiratory tract infections (VRTIs), mainly coronaviruses, have seriously affected human health worldwide in recent years. In this review, we presented the relevant data which originated from trusted publishers regarding the practical benefits of functional foods (FFs) and their dietary sources, in addition to natural plant products, in viral respiratory and COVID-19 prevention and immune-boosting activities. As a result, FFs were confirmed to be functionally active ingredients for preventing COVID-19 and VRTIs. Furthermore, the antiviral activity and immunological effects of FFs against VRTIs and COVID-19 and their potential main mechanisms of action are also being reviewed. Therefore, to prevent COVID-19 and VRTIs, it is critical to identify controlling the activities and immune-enhancing functional food constituents as early as possible. We further aimed to summarize functional food constituents as a dietary supplement that aids in immune system boosting and may effectively reduce VRTIs and COVID-19 and promote therapeutic efficacy.
... Excess Zn 2+ can also impair the immune system and allow pathogens to evade both innate and adaptive responses (Rink and Kirchner 2000). It is thus feasible that the undesirable effects of excessively low or high Zn 2+ concentrations may be mitigated through the use of metal carrier proteins to provide proper regulation of Zn 2+ -dependent proteins, or that chelation of excess Zn 2+ by metal carrier proteins could be employed to treat autoimmune diseases such as rheumatoid arthritis by inhibiting the function of lymphocytes (Skrajnowska and Bobrowska-Korczak 2019). ...
Article
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Zn²⁺ ions are essential in many physiological processes, including enzyme catalysis, protein structural stabilization, and the regulation of many proteins. The affinities of proteins for Zn²⁺ ions span several orders of magnitude, with catalytic Zn²⁺ ions generally held more tightly than structural or regulatory ones. Metal carrier proteins, most of which are not specific for Zn²⁺, bind these ions with a broad range of affinities that overlap those of catalytic, structural, and regulatory Zn²⁺ ions and are thought to be responsible for distributing the metal through most cells, tissues, and fluid compartments. While little is known about how many proteins obtain or release these ions, there is now considerable experimental evidence suggesting that metal carrier proteins may be responsible for transferring metals to and from some Zn²⁺-dependent proteins, thus serving as a major regulatory factor for them. In this review, the biological roles of Zn²⁺ and structures of Zn²⁺ binding sites are examined, and experimental evidence demonstrating the direct participation of metal carrier proteins in enzyme regulation is discussed. Mechanisms of metal ion transfer are also offered, and the potential physiological significance of this phenomenon is explored.
... A major cause of CAP is compromised immune function [7]. Zinc (Zn) is required for proper immune function [8][9][10], and an insufficient dietary intake is highly prevalent within vulnerable populations [11,12]. Zndeficient subjects are more susceptible to bacterial and viral pathogens [13] and have a higher incidence of pneumonia [14][15][16] while Zn supplementation can reduce the incidence of pneumonia [17][18][19]. ...
Article
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Pneumococcal pneumonia is a leading cause of morbidity and mortality worldwide. An increased susceptibility is due, in part, to compromised immune function. Zinc is required for proper immune function, and an insufficient dietary intake increases the risk of pneumonia. Our group was the first to reveal that the Zn transporter, ZIP8, is required for host defense. Furthermore, the gut microbiota that is essential for lung immunity is adversely impacted by a commonly occurring defective ZIP8 allele in humans. Taken together, we hypothesized that loss of the ZIP8 function would lead to intestinal dysbiosis and impaired host defense against pneumonia. To test this, we utilized a novel myeloid-specific Zip8KO mouse model in our studies. The comparison of the cecal microbial composition of wild-type and Zip8KO mice revealed significant differences in microbial community structure. Most strikingly, upon a S. pneumoniae lung infection, mice recolonized with Zip8KO-derived microbiota exhibited an increase in weight loss, bacterial dissemination, and lung inflammation compared to mice recolonized with WT microbiota. For the first time, we reveal the critical role of myeloid-specific ZIP8 on the maintenance of the gut microbiome structure, and that loss of ZIP8 leads to intestinal dysbiosis and impaired host defense in the lung. Given the high incidence of dietary Zn deficiency and the ZIP8 variant allele in the human population, additional investigation is warranted to improve surveillance and treatment strategies.
... Zinc has an antagonistic effect on the toxicity of cadmium and copper [13,16]. A lack of zinc may lead to impaired immune function and tumor development [17][18][19]. An increased prevalence of obstructive lung disorder was observed among individuals with low zinc intake regardless of smoking status, and the adjusted odds of lung disorder are approximately 1.9 times greater for subjects in the lowest zinc-intake tertile than those in the highest tertile (odds ratio = 1.89, 95% confidence interval = 1.22-2.93) ...
Article
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The effects of metal on pulmonary function are inconsistent, and abnormal distribution of metals can decrease lung function. However, the effects of metals exposure on chronic obstructive pulmonary disease (COPD) are still unclear. This study aims to explore the relationship between metal exposure and COPD risk. Cross-sectional data from the National Health and Nutrition Survey (NHANES) 2015–2016 was analyzed. Inductively coupled plasma dynamic reaction cell mass spectrometry (ICP-DRC-MS) was used to measure the metals concentration in the blood. The multiple linear regression and restricted cubic spline (RCS) were used to analyze the relationship between metals exposure and COPD risk. In this study, 1399 participants were included, of which 107 participants were diagnosed with COPD using self-reported chronic bronchitis, emphysema, and COPD. The second and third tertiles of copper increased the COPD risk by 1.98-fold (95% CI: 1.08–3.62) and 2.43-fold (95% CI: 1.32–4.48) compared with the first tertile, using p = 0.005 for the trend after adjusting for the covariates. RCS showed a positive linear correlation between copper and COPD risk (p = 0.006 for overall association) in all participants. When stratified by sex, the multi-factor analysis showed that the third tertile of copper increased male’s COPD risk by 3.42-fold (95% CI: 1.52–7.76), with p = 0.003 for the trend, and RCS also showed a positive linear correlation (p = 0.013 for overall association). Although RCS showed that selenium can reduce the COPD risk (p = 0.008 for overall association) in males, an association between selenium and COPD was not observed (p > 0.05). Our findings suggest that a high concentration of copper may increase COPD risk in males in the general US population, and more research is needed to explore its possible mechanism of action.
... On the other hand, IFNs can stimulate the influx of zinc into the target cells. Decreased levels of IL-10 positively affect macrophage function and Th1 response [81,85,86]. IFNα antiviral activity is mediated through JAK1/STAT1 downstream signaling and upregulation of antiviral enzymes, including protein kinase RNA-activated (PKR) and latent ribonuclease (RNaseL) [87]. ...
Article
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The concern of today's communities is to find a way to prevent or treat COVID-19 and reduce its symptoms in the patients. However, the genetic mutations and more resistant strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerge; the designed vaccines and adjuvant therapies would potentially control the symptoms and severity of COVID-19. The most important complication of this viral infection is acute respiratory distress syndrome, which occurs due to the infiltration of leukocytes into the alveoli and the raised cytokine storm. Interferons, as a cytokine family in the host, play an important role in the immune-related antiviral defense and have been considered in the treatment protocols of COVID-19. In addition, it has been indicated that some nutrients, including vitamin D, magnesium and zinc are essential in the modulation of the immune system and interferon (IFN) signaling pathway. Several recent studies have investigated the treatment effect of vitamin D on COVID-19 and reported the association between optimal levels of this vitamin and reduced disease risk. In the present study, the synergistic action of vitamin D, magnesium and zinc in IFN signaling is discussed as a treatment option for COVID-19 involvement.
... Zinc induces isolated leukocytes to produce cytokines. It also induces the production of interleukin-1, interleukin-6, and tumor necrosis factor-α by monocytes [14]. Also, IL-2 is involved in the activation of NK and Tcytotoxic cells. ...
Article
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Cutaneous Leishmaniasis (CL) is an endemic parasitic infection caused by various Leishmania species, with a specific predisposition of each species into a particular geographical area. Cutaneous lesions can either be a single, limited skin lesion or multiple, large, locally destructions skin lesions. Several therapies are proposed for CL, but severe side effects, high costs, and incomplete efficacy make researchers find replaceable therapies. Since the usage of zinc sulfate as a therapeutic agent has a long history in treating of various dermatological diseases, Zinc plays an essential role in the development and function of innate immunity cells (neutrophils and natural killer cells), which play significant roles in killing parasites. It also has a significant inhibitory effect on key enzymes involved in the carbohydrate metabolism and virulence of L. major and L.tropica. Therefore, its use as an oral therapy for CL might represent a significant addition to the armamentarium of anti-leishmanial medications. This review summarizes and discusses previous and recent findings regarding the therapeutic roles of oral zinc sulfate in cutaneous leishmaniasis therapy.
... In the case of adaptive immunity, zinc deficiency causes T-and B-cell lymphopenia, imbalance among the different helper T cell subsets, and defective antibody production (7)(8)(9). In addition, cytokine production is markedly influenced by zinc deficiency in both innate and adaptive immune cells (10,11). Clinically, zinc deficiency caused by malnutrition and dyshomeostasis results in increased host susceptibility to various infections (12). ...
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The essential microelement zinc plays immunoregulatory roles via its ability to influence signaling pathways. Zinc deficiency impairs overall immune function and resultantly increases susceptibility to infection. Thus, zinc is considered as an immune-boosting supplement for populations with hypozincemia at high-risk for infection. Besides its role as a structural cofactor of many proteins, zinc also acts as an intracellular messenger in immune cell signaling. T-cell activation instructs zinc influx from extracellular and subcellular sources through the Zip6 and Zip8 zinc transporters, respectively. Increased cytoplasmic zinc participates in the regulation of T-cell responses by modifying activation signaling. However, the mechanism underlying the activation-dependent movement of zinc ions by Zip transporters in T cells remains elusive. Here, we demonstrate that Zip6, one of the most abundantly expressed Zip transporters in T cells, is mainly localized to lipid rafts in human T cells and is recruited into the immunological synapse in response to TCR stimulation. This was demonstrated through confocal imaging of the interaction between CD4+ T cells and antigen-presenting cells. Further, immunoprecipitation assays show that TCR triggering induces tyrosine phosphorylation of Zip6, which has at least three putative tyrosine motifs in its long cytoplasmic region, and this phosphorylation is coupled with its physical interaction with Zap70. Silencing Zip6 reduces zinc influx from extracellular sources and suppresses T-cell responses, suggesting an interaction between Zip6-mediated zinc influx and TCR activation. These results provide new insights into the mechanism through which Zip6-mediated zinc influx occurs in a TCR activation-dependent manner in human CD4+ T cells.
... Zinc deficiency in the innate immune system is characterized by reduced chemotaxis of polymorphonuclear cells (PMNs) and phagocytosis of macrophages, with a resultant diminishment in production of pathogen-neutralizing reactive oxygen species (ROS) (Bonaventura et al., 2015). Moreover, the production of proinflammatory cytokines by monocytes is apparently impaired under zinc deficiency (Rink and Kirchner, 2000), suggesting an essential role of zinc in regulating, and potentially restoring, innate immune responses (Gao et al., 2018;Haase and Rink, 2007;Sapkota and Knoell, 2018). ...
Article
Zinc is an essential micronutrient with crucial roles in multiple facets of biological processes. Dysregulated zinc homeostasis impairs overall immune function and resultantly increases susceptibility to infection. Clinically, zinc supplementation is practiced for treatment of several infectious diseases, such as diarrhea and malaria. Recent focus on zinc as a beneficial element for immune system support has resulted in investigation of the immunomodulatory roles of zinc in a variety of immune cells. Besides its classical role as a cofactor that regulates the structural function of thousands of proteins, accumulating evidence suggests that zinc also acts, in a manner similar to calcium, as an ionic regulator of immune responses via participation as an intracellular messenger in signaling pathways. In this review, we focus on the role of zinc as a signaling molecule in major pathways such as those downstream of Toll-like receptors-, T cell receptor-, and cytokine-mediated signal transduction that regulate the activity and function of monocytes/macrophages and T cells, principal players in the innate and adaptive immune systems.
... Zinc levels were lower in LO, especially around calving. During the acute-phase response, zinc is sequestered into hepatocytes by metallothionein, the synthesis of which is enhanced by proinflammatory cytokines (Rink and Kirchner, 2000). ...
Article
The dry-off of dairy cows represents an important phase of the lactation cycle, influencing the outcome of the next lactation. Among the physiological changes, the severity of the inflammatory response can vary after the dry-off, and this response might have consequences on cow adaptation in the transition period. The plasma protein profile is a diagnostic tool widely used in humans and animals to assess the inflammatory status and predict the outcome of severe diseases. The albumin-to-globulin ratio (AG) can represent a simple and useful proxy for the inflammatory condition. In this study, we investigated the relationship between AG before dry-off and inflammation, metabolic profile, and performance of 75 Holstein dairy cows. Blood samples were collected from −62 (7 d before dry-off) to 28 d relative to calving (DFC) to measure metabolic profile biomarkers, inflammatory variables, and liver function. Daily milk yield in the first month of lactation was recorded. Milk composition, body condition score, fertility, and health status were also assessed. The AG calculated 1 wk before dry-off (−62 DFC) was used to retrospectively group cows into tertiles (1.06 ± 0.09 for HI, 0.88 ± 0.04 for IN, and 0.72 ± 0.08 for LO). Data were subjected to ANOVA using the PROC MIXED program in SAS software. Differences among groups observed at −62 DFC were almost maintained throughout the period of interest, but AG peaked before calving. According to the level of acute-phase proteins (haptoglobin, cerulo-plasmin, albumin, cholesterol, retinol-binding protein), bilirubin, and paraoxonase, a generally overall lower inflammatory condition was found in HI and IN than in the LO group immediately after the dry-off but also after calving. The HI cows had greater milk yield than LO cows, but no differences were observed in milk composition. The somatic cell count reflected the AG ratio trend, with higher values in LO than IN and HI either before dry-off or after calving. Fertility was better in HI cows, with fewer days open and services per pregnancy than IN and LO cows. Overall, cows with high AG before dry-off showed an improved adaptation to the new lactation, as demonstrated by a reduced systemic inflammatory response and increased milk yield than cows with low AG. In conclusion, the AG ratio before dry-off might represent a rapid and useful proxy to evaluate the innate immune status and likely the ability to adapt while switching from the late lactation to the nonlactating phase and during the transition period with emphasis on early lactation.
... Immune protection is based on 2 major cell classes, namely innate and adaptive immune cells. 13 The innate immune system has immediate responsiveness. The cells are generally sustained by the granulocytes and macrophages of neutrophils, which directly entrap various pathogens, like viruses and bacteria. ...
Coronavirus disease 2019 (COVID-19) is a recently emerged pandemic caused by a novel virus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This disease is communicable and mainly affects the respiratory tract. The outbreak of this disease has greatly influenced human health and economic activities worldwide. The absence of any medication for this infection highlights the urgent need for the development of alternative methods for managing the spread of the disease. Our immune system operates based on a complex array of cells, processes, and chemicals that continuously protect our body from invading pathogens, including viruses, toxins, and bacteria. The present study was conducted to perform a comprehensive review of all dietary treatments for boosting immunity against viral infections. No study was found to explicitly support the use of any healthy foods or supplements to protect against COVID-19. However, this study offers details on well-researched functional foods and supplements that typically improve the immune response, which could be helpful against this newly emerged pandemic.
... Flow cytometry measurements showed that the minimal mole fraction PS necessary for An-5 binding decreases in the presence of PEA (Stuart et al., 1998). It is also worth mentioning that zinc ions [Zn 2+ ] at concentration of 12-16 µmol/L probably influence the An-5 binding to PS by increasing affinity between An-5 and PS (Rink, Kirchner, 2000). One can therefore assume that An-5 -PS binding depends on the environment in a cell membrane. ...
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The next book in the series Advances in Biomedical Research edited by L. Bialy and I. Mlynarczuk-Bialy and . This book contains chapters dealing various topics in biomedicine including COVID and humanistic aspects of medicine.
... Immune protection is based on 2 major cell classes, namely innate and adaptive immune cells. 13 The innate immune system has immediate responsiveness. The cells are generally sustained by the granulocytes and macrophages of neutrophils, which directly entrap various pathogens, like viruses and bacteria. ...
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Coronavirus disease 2019 (COVID-19) is a recently emerged pandemic caused by a novel virus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This disease is communicable and mainly affects the respiratory tract. The outbreak of this disease has greatly influenced human health and economic activities worldwide. The absence of any medication for this infection highlights the urgent need for the development of alternative methods for managing the spread of the disease. Our immune system operates based on a complex array of cells, processes, and chemicals that continuously protect our body from invading pathogens, including viruses, toxins, and bacteria. The present study was conducted to perform a comprehensive review of all dietary treatments for boosting immunity against viral infections. No study was found to explicitly support the use of any healthy foods or supplements to protect against COVID-19. However, this study offers details on well-researched functional foods and supplements that typically improve the immune response, which could be helpful against this newly emerged pandemic. Altern Ther Health Med. 2020 Dec 29; AT6564. Online ahead of print
... Flow cytometry measurements showed that the minimal mole fraction PS necessary for An-5 binding decreases in the presence of PEA (Stuart et al., 1998). It is also worth mentioning that zinc ions [Zn 2+ ] at concentration of 12-16 µmol/L probably influence the An-5 binding to PS by increasing affinity between An-5 and PS (Rink, Kirchner, 2000). One can therefore assume that An-5 -PS binding depends on the environment in a cell membrane. ...
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Alginate is a polysaccharide naturally occurring in brown seaweeds cell walls. Unique properties such as ease of gelation, biodegradability, biocompatibility, and non-toxicity of alginates make them widely employed in a variety of industries. Mentioned here properties and versatility of alginate resulted in approval by U.S. FDA (Food and Drug Administration), thereby initiating its application in the biomedical sector on an industrial scale. The chemical modifications of this biopolymer allow to obtain different forms (e.g., hydrogels, films, fibers), as well as to receive the desired characteristic. The challenge is to match the physical properties to the specific application requirements. Alginates are often utilized in the pharmaceutical industry in the controlled drug delivery and as protein carriers. Moreover, alginates can be a component of drugs for obesity and reflux. They are also used in wound healing due to water retention capability, anticancer and antimicrobial properties. On account of the similarity of alginate hydrogels to living tissues, elasticity and soft structure, their successful application in vitro, in tissue engineering or regenerative medicine is possible. Alginate hydrogel can be widely used as a bioink for 3-D bioprinting. The manufactured alginate scaffolds may be a matrix that provides a suitable substrate for cell growth and cell protection against possible external damages by customization of mechanical properties. Although it is feasible to control the mechanical properties at the alginate extraction stage or during hydrogel cross-linking process, alginate hydrogels have very limited overall physical properties, mainly mechanical stiffness. The possibility to obtain accurately regulated chemical and physical properties of alginate based material may lead to a revolution in the biomedical sciences.
... Flow cytometry measurements showed that the minimal mole fraction PS necessary for An-5 binding decreases in the presence of PEA (Stuart et al., 1998). It is also worth mentioning that zinc ions [Zn 2+ ] at concentration of 12-16 µmol/L probably influence the An-5 binding to PS by increasing affinity between An-5 and PS (Rink, Kirchner, 2000). One can therefore assume that An-5 -PS binding depends on the environment in a cell membrane. ...
Chapter
Melatonin and noradrenaline are the hormones responsible for the regulation of the sleep. The hormones’ interplay occurs on three levels – neuronal, physiological, and biochemical. REM-ON and REM-OFF neurons remain under the regulation by noradrenaline. Moreover, the increased concentration of noradrenaline in the brain tissue, by the upregulation of the hormone’s transporters, leads to the increased excitability of the brain, the downregulation of melatonin biosynthesis, and eventually to the lack of sleep. The biosynthesis pathways of both hormones involve the same enzyme – Monoamine oxidase (MAO), thus their interaction might appear on the biochemical level. The dysregulation of melatonin and noradrenaline concentration has an impact on the progression and development of severe physiological complications, such as diabetes or even cancer. The review focuses on the detailed description of metabolic pathways where melatonin and noradrenaline can interact and cause the modulation of the sleep – in particular REM sleep phase. In the end, all the data is connected with the clinical disorders concerning the melatonin-noradrenaline equilibrium dysregulation.
... The lower plasma zinc concentration in cows that developed a uterine disease could suggest a more severe inflammatory status. It has been reported that the plasma zinc concentration is reduced during the acutephase reaction because of increased liver synthesis of metallothionein, which sequesters zinc from blood to reduce pathogen survival (Rink and Kirchner, 2000;Trevisi and Minuti, 2018). In this study, retinol concentrations were lower in sick cows, especially at 7 DFC, suggesting a reduction of carrier proteins (retinol-binding proteins) as a result of the acute-phase response (Bertoni and Trevisi, 2013). ...
Article
The objective of this study was to assess how uterine disorders alter the lying behaviour and plasma biomarkers in dairy cows. 34 multiparous cows were retrospectively classified into three groups according to the first uterine disorder that cows were diagnosed with: retained placenta (RP), metritis (MET), or healthy (H; cows without any clinical disease). Lying time (LT) and duration of lying bouts (LB) were monitored between 6 weeks prior to and 8 weeks after calving via the AfiAct II pedometer. Blood samples were collected routinely between 14 days before and 28 days after calving. Data was analysed using Proc MIXED of SAS ver. 9.4. Regardless of grouping, both LT and LB were longer (P < 0.01) in the prepartum period (774 ± 16.6 min/day and 89.9 ± 2.1 min/bout) than in the first 28 days after calving (DFC; 653 ± 16.7 min/day and 63.7 ± 2.1 min/bout). Cows with RP had longer LT than healthy cows during the last 3 weeks before calving (837 ± 30.9 vs. 735 ± 27.1 min/day; P < 0.05). LT in cows with MET and healthy cows were not significantly different. The LB was similar among groups, averaging 76.1 ± 3.4 min/bout in healthy cows, 73.2 ± 3.8 min/bout in cows with RP, and 75.2 ± 3.7 min/bout in cows with MET (P > 0.05). Compared with healthy cows, cows with RP laid down longer and stood up for shorter times (P < 0.05), particularly before calving. In addition, cows with RP had increased mobilization of body stores and more pronounced inflammatory status, as demonstrated by plasma haptoglobin (P = 0.04) and albumin (P < 0.01) concentrations. Our data suggest that automatic monitoring of lying behaviour could help identify cows at increased risk of developing certain disorders, such as RP.
... Zinc is one of the most important trace elements required as a catalytic, structural, and regulatory ion for the activities of more than 300 enzymes, proteins, and transcriptional factors (15) . Therefore, zinc is a key element in many homeostatic responses of the body, including oxidative stress and in many biological functions, including immune efficiency (16) . Zinc keeps hormone like estrogen, progesterone and testosterone levels stable throughout the entire menstrual cycle. ...
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Background Polycystic ovary syndrome (PCOS) is the most common endocrine-metabolic disorder affecting women of reproductive age characterized by multiple hormonal imbalances, reflecting on a clinical presentation dominated by manifestations of hyperandrogenism, which generate short and long term consequences on female health. Skin is a major target for androgen activity, several hyperandrogenemia-triggered dermatologic alterations can be seen in PCOS, most commonly hirsutism, androgenic alopecia, acne, seborrhea, onycholysis, and onychorrhexis. Zinc is one of the most important trace elements required as a catalytic, structural, and regulatory ion for the activities of more than 300 enzymes, proteins, and transcriptional factors. Zinc insufficiency in the female can lead to complications such as impaired synthesis/secretion of follicular stimulating hormone (FSH) and luteinizing hormone (LH), abnormal ovarian development. Objective To assess serum zinc level in patients with PCOS. Methods A case-controlled study was conducted in Al-Imamein Al-Kadhemein Medical City from the period of March to June 2016. Eighty females were enrolled in this study; their age ranged from 20 to 32 years. They were divided into 4 groups: Group I: Twenty patients with PCOS with body mass index (BMI) ranged from 30.0-40.0. Group II: Twenty normal healthy control obese ladies with BMI ranged from 30.0-40.0. Group III: Twenty patients with polycystic ovary syndrome with BMI ranged from 18.5-29.9. Group IV: Twenty females as a healthy control non-obese ladies with BMI ranged from 18.5-29.9. Results Serum zinc level was significantly decreased in obese PCO group than in non-obese PCO group. Serum prolactin (PRL) level and LH levels were elevated in PCO group which was highly significant. There was negative correlation between serum zinc level and BMI in PCO patients. Also, negative correlation was observed between serum zinc level and serum PRL level in non-obese PCO patients. Conclusion Serum zinc level reduced in obese PCOS than in non-obese PCO. Keywords Serum zinc level, polycystic ovary syndrome
... Zinc is one of the most important trace elements required as a catalytic, structural, and regulatory ion for the activities of more than 300 enzymes, proteins, and transcriptional factors (15) . Therefore, zinc is a key element in many homeostatic responses of the body, including oxidative stress and in many biological functions, including immune efficiency (16) . Zinc keeps hormone like estrogen, progesterone and testosterone levels stable throughout the entire menstrual cycle. ...
Article
Background Polycystic ovary syndrome (PCOS) is the most common endocrine-metabolic disorder affecting
... As a cofactor of more than 300 enzymes, zinc contributes to normal function of many organs and tissues. It is also involved in the modulation of immune system mechanisms (2)(3)(4) . It enhances immune responses, among other things, by inducing monocyte adhesion to vascular endothelial cells, whereas a reverse effect is seen for its complexes with phosphates. ...
... Another study conducted by León-Cañedo et al. (2017) found that the main source of Cu and Zn metals in a simulated culture system with L. vannamei was the diet, which accounted for 91.8% of Cu and 97.0% of Zn. Zn is known as an essential nutrient for many physiological functions, such as growth, development (Watanabe et al. 1997), and immune function (Rink and Kirchner 2000). Similarly, Lin et al. (2013) found that zinc significantly reduced the cumulative mortality of L. vannamei against Vibrio harveyi, indicating an enhancement of the immune system and hence an improved resistance of the shrimp. ...
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The occurrence and contamination level of seven important toxic metals (Cd, Cu, Co, Cr, Hg, Pb, and Zn) and three additional metals (Al, Fe, and Mn) in the water, sediment, and shrimp muscle in aquaculture areas located in Central Java, Indonesia, were investigated. The results suggest that the majority of metals have higher concentrations in the inlet followed by the outlet and ponds. Cd dissolved in the waters exhibited the highest level in Pekalongan (3.15 ± 0.33 μg L−1). Although Pb was not detected in the water, it was detected in the sediment, and the concentration ranged from 7.6 to 15.40 mg kg−1 dw. In general, the heavy metal concentrations in the sediments were found to decrease in the sequence Al > Fe > Mn > Zn > Cr > Cu > Co > Pb. Concentrations below the effects range low level based on the Canadian sediment quality guidelines were found for Cr, Cu, Pb, and Zn, whereas moderate sediment pollution (25–75 mg kg−1 dw) was observed for Cr (all regions), Cu (except in the Pekalongan region), and Zn (Brebes and Tegal regions) according to the US EPA standard. The status of the waters was evaluated by calculating a pollution index derived mostly from Mn and Zn. The ecological risk (geoaccumulation index (Igeo), contamination factor (CF), pollution load index (PLI), and potential ecological risk index (ERI)) determined in the sediments indicated that all studied areas had low to moderate contamination. The concentrations of all metals in shrimp were generally below the maximum limits for seafood, except for Zn (in all stations), Pb, and Cr (Tegal and Pekalongan). The hazard index values for metals indicated that consuming shrimp would not have adverse effects on human health.
... Zinc is absorbed along the length of the small intestine by a poorly characterized transport mechanism ((zinc is transported in part by albumin), but is also excreted in intestinal and pancreatic secretions. Zinc deficiency is thought to be relatively common in patients with chronic diarrhea, malabsorption, and hypermetabolic states (sepsis, burns) 22 . Zinc has been shown to be decreased in neutrophils both in patients with active Chrons Disease and those with Ulcerative Colitis. ...
Article
Bone metabolism changes in patients with inflammatory bowel disease (IBD) awoke a growing interest in the past few years mostly because of their high prevalence, with estimations around 40 osteoporosis. Contributing factors including inadequate nutrition, corticosteroid, and decreased physical activity elements play an important role in the growth development and maintenance of bones. The aim of our study was to assess the Bone mineral indexes and correlation with bone mineral density healthy Controls of both gender processed for all baseline parameters. Serum Zinc, Copper and Selenium assessed by Atomic Absorption Spectrophotometry. The subjects were evaluated for Bone Mineral Dens Absorptiometry scan and T score was calculated to assess Osteoporosis. Pearson correlation tests were used for statistical analysis Bone Mineral Density than the Controls. Bone Mineral Density values were not different between the subtypes Disease and Ulcerative Colitis. Though Ulcerative Colitis and Crohn's Disease patients had significantly lower Bone Mineral Density than the Controls. Significantly Low Zinc and selenium level was observed in Inflammatory Bowel disease patients however Copper was found significantly high. correlated with Bone Mineral Den develop metabolic bone disease. Along with other nutrients supplement Zinc, Copper and Selenium should be added to prevent bone loss as well as oxidative stress in Inflamma
... In Myanmar, morbidity of high blood pressure increases from 18 percent to 31 percent in male and from 16 Zinc is involved in numerous metabolic pathways as a cofactor for more than 300 enzymes 3 . Blood pressure levels (both systolic and diastolic) were negatively correlated with zinc-dependent enzymes such as super oxide dismutase, lysyl oxidase and alkaline phosphatase 4 . It was reported that zinc deficiency causes the arteries to become hard, brittle and often inflamed. ...
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Hypertension is one of the most prevalent diseases in developing as well as developed countries. Macro and micro nutrients are known to play a major role in various enzyme reactions directly related to blood pressure regulation. Imbalance of copper and zinc level might be involved in pathogenesis of essential hypertension. This study aimed to investigate serum copper level, zinc level and copper/zinc ratio in hypertensive subjects (n = 40) of age 30-60 years. For comparison, apparently healthy normotensive subjects (n = 40) were also recruited. Serum copper and zinc levels were measured by Graphite Furnace-Atomic Absorption Spectrophotometry (GF-AAS) and copper/zinc ratio was calculated. Serum copper level of the hypertensive subjects (150.60 ± 31.64 µg/dL) was significantly higher than that of the normotensive subjects (76.97 ± 22.38 µg/dL) (P < 0.001) whereas serum zinc level of hypertensive subjects (57.16 ± 42.09 µg/dL) was significantly lower than that of the normotensive subjects (96.17 ± 42.77 µg/dL) (P < 0.001). Serum copper/zinc ratio in hypertensive subjects (3.30 ± 1.32) was significantly higher than that of normotensive subjects (0.90 ± 0.33) (P < 0.001). Serum copper level, serum zinc level and serum copper/zinc ratio were significantly (n = 80, P < 0.001) correlated with mean arterial blood pressure (r =-0.38, r = 0.78, r = 0.73) respectively. It has been noted that increased serum copper level, reduced serum zinc level and increased serum copper/zinc ratio might be associated with blood pressure.
... LPx levels were elevated due to blood glucose which leads to the formation of reactive oxygen species [25]. The pro-immune property of zinc and the antioxidant activity of phenolics present in the ZnO NPs could have attributed to the increased levels of antioxidant enzymes CAT and SOD in ZnO NPtreated rats [26]. Phenolic content present in SC seeds has been previously reported to have antihyperglycaemic and antihyperlipidaemic effects on diabetes-induced rats [27,28] and also prevents insulin resistance, lipid and glucose dysregulation [29,30]. ...
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Sulphonylureas are extensively used in the treatment of type II diabetes; however, these drugs have complications of hypoglycaemia and weight gain. The current study aims at developing a potent antidiabetic drug that has lesser side effects and better management of its associated conditions. Zinc oxide nanoparticles (ZnO NPs) were synthesised using Syzygium cumini seed extract with an average size of 18.92 nm. In vitro studies on rat insulinoma (RIN-5F) cells revealed that cells treated with synthesised ZnO NPs showed a dose-dependent increase in insulin secretion. Streptozotocin-fructose-induced type II diabetic rats treated with ZnO NPS exhibited a significant reduction (p < 0.01) in the blood glucose levels, total cholesterol, triglycerides, and low-density lipoprotein levels and increase (p < 0.01) in serum insulin and liver antioxidant enzyme levels proclaiming its role as a hypoglycaemic and hypolipidaemic drug. Treatment of ZnO NPs in diabetic rats exhibited an increased number of beta cells which was responsible for its increased insulin levels and reduced glucose levels. From the overall observations, biosynthesised ZnO NPs exhibited an efficacious hypoglycaemic effect in diabetic rats, so it can be suggested as a potent antidiabetic drug.
... Згідно із сучасним уявленням, кожній патології властиві певні відхилення в мікроелементному складі. При цьому дисбаланс елементного гомеостазу не просто супроводжує, а й провокує розвиток різноманітних захворювань, потенціює перебіг, переводить їх у хронічну форму [9]. так, цинк -життєво важливий елемент, один з найпоширеніших мікроелементів організму, кількісно -другий після заліза. ...
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The objective: to study the state of the prooxidant system and the system of antioxidant protection in patients with acute epididymitis and the content of essential elements as Zn and Cu in these patients. Маterials and methods. To determine the activity of antioxidant enzymes and essential microelementes, 120 patients with acute epididymitis were surveyed in the Urological Clinic of National Military–Medical Clinical Centre «GVKG». The patients were divided into 4 Groups: Group І (n=40) – patients, suffering from acute epididymitis, were treated according to the guidelines, Group ІІ (n=40) – patients, suffering from acute epididymitis, whose treatment included an antibiotic ofloxacin, Group ІІІ (n=40) – patients, suffering from acute epididymitis, whose complex of the treatment included an antibiotic ofloxacin, l-arginine and suppositories, which contains a fibrinolytic – streptokinase (15,000 IU) and proteolytic – streptodornase (1 250 IU), Group control – n=20 conditionally healthy patients. Results. It was found that there is a significant dependence between the content of Zn, Cu in blood and enzymes of the system of antioxidant protection. Conclusion. Metabolic changes in the presence of a decrease of Zn and excess Cu correlate with an imbalance in the system of antioxidant protection, namely the decrease in the level of antioxidant defense enzymes and excess the level of products of oxidative modification of proteins.
... Zinc is an important trace element for animals, functioning largely or entirely in enzyme systems and being involved in protein synthesis, carbohydrate metabolism, and many other biochemical reactions (Rink and Kirchner, 2000). Zinc is associated with more than 300 enzymes either as component or as activator.Zinc is an essential trace mineral that serves some roles in an animal's body such as the controlling of growth by affecting on feed intake, secretion of mitogenic hormones, gene expression of proteins (Huerta et al., 2002).The most widely used products for zinc supplementation are inorganic (zinc sulfate and zincoxide), and recently, organically bound zinc supplements are being used in animal diets (Saeidet al., 2010). ...
... These findings are in line with some previous studies. The same findings were reported at room temperature [58]. Furthermore, SeZnP supplementation increased IL-2, IL-6, and IL-8 and decreased IL-10 concentration compared to P, ZnP and SeP supplementation, suggesting that SeZnP is more effective in elevation of Wistar rat's immune function than P, ZnP and SeP. ...
Article
Aims: The present study was carried out to investigate the influences of Selenium/Zinc-Enriched probiotics (SeZnP) on growth performance, serum enzyme activity, antioxidant capability, inflammatory factors and gene expression associated with Wistar rats inflated under high ambient thermal-stress. Main methods: Sixty male rates with six-weeks of age were randomly allocated into five groups (12 per group) and fed basal diet (Control), basal diet supplemented with probiotics (P), Zinc-Enriched probiotics (ZnP, 100 mg/L), Selenium-Enriched Probiotics (SeP, 0.3 mg/L) and Selenium/Zinc-Enriched probiotics (SeZnP, 0.3 mg + 100 mg/L). The experiment lasted 30 days. Blood and Tissues samples were taken to investigate serum enzyme activity, antioxidants capability and inflammatory factors by using of commercial kits and antioxidant, heat shock and inflammatory related molecules expressions were determined by qRT-PCR. Key findings: Data analysis revealed that thermal stress significantly increased the level of Aspartate-aminotransferase, Alanine-aminotransferase, Lactate-dehydrogenase, Creatine-kinase, blood urea nitrogen, Creatinine and Alkaline phosphatase compared to P, ZnP, SeP or SeZnP groups (P < 0.01). However, supplementation of ZnP, SeP, and SeZnP significantly enhanced glutathione content, glutathione-peroxidase & superoxide-dismutase activity, and decreased malondialdehyde content (P < 0.05). Moreover, the concentration of IL-2, IL-6 and IL-8 were significantly increased while IL-10 was significantly decreased (P < 0.05). Furthermore, the expression of GPx1 and SOD1 genes were significantly increased, but COX-2, iNOS, HSP70 and 90 mRNA levels were significantly decreased (P < 0.05). Finally, the highest influence of the mentioned parameters was observed in SeZnP supplemented group. Significance: Our study suggests that SeZnP supplementation serves as possible and best nutritive than ZnP or SeP for Wistar rats raising under high ambient temperature.
... Shrimp fed the diets supplemented with inorganic or organic zinc had significantly higher activities of Cu-Zn SOD in hemolymph and hepatopancreas than those fed the diet with no-supplemented zinc, moreover, shrimp fed the diets supplemented with organic zinc had significantly higher Cu-Zn SOD activity in hepatopancreas than those fed the I-Zn diet, which proved that organic zinc could heighten the catalytic effect of the disproportionation of superoxide anion radicals compared to inorganic zinc. In addition to preventing oxidation, zinc also plays a vital role in the immune system (Rink and Kirchner, 2000). PO, AKP, ACP and LZM play crucial functions in the immune system (Apines-Amar et al., 2004;Tan and Mai, 2001). ...
Article
An 8-week feeding trial was conducted to investigate the effects of different dietary dosage forms of zinc on growth performance, meat quality, antioxidant and immune capacity of juvenile Pacific white shrimp, Litopenaeus vannamei. Four isonitrogenous and isolipidic diets were formulated to contain different dosage forms of zinc, the control diet (no-supplemented zinc), I-Zn diet (120 mg kg⁻¹ zinc from zinc sulfate), M-Zn diet (60/60 mg kg⁻¹, zinc sulfate/zinc amino acid complex = 1:1) and Availa-Zn diet (60 mg kg⁻¹ zinc from zinc amino acid complex), respectively. A total of 480 shrimp juveniles with initial weight 1.84 ± 0.02 g were randomly divided into four diets with four replications, each replication consisted of 30 shrimp. The results revealed that shrimp fed the M-Zn diet had significantly higher percent weight gain (PWG), specific growth rate (SGR), feed efficiency (FE), protein efficiency ratio (PER) and protein retention efficiency (PRE) than those fed the other diets. The significantly higher concentration of glucose (GLU) in hemolymph was observed in shrimp fed the M-Zn diet. Shrimp fed the diets supplemented with zinc amino acid complex had significantly lower values of drip and thawing losses of whole shrimp or muscle compared to those fed the control and I-Zn diets, which indicated that shrimp fed the diets supplemented with zinc amino acid complex had a better water-holding capacity. Moreover, shrimp fed the Availa-Zn diet had significantly higher the activities of alkaline phosphatase (AKP), acid phosphatase (ACP) and lysozyme (LZM) in hepatopancreas than those fed the control and I-Zn diets. Meanwhile, shrimp fed the M-Zn and Availa-Zn diets showed an up-regulation of expression levels of Cu-Zn sod, akp, acp and lzm in hepatopancreas. Principal component analysis (PCA) and multivariate correlation analysis demonstrated that shrimp fed the experimental diets exhibited significant variations and shrimp fed the M-Zn diet showed better growth response and meat quality. These findings could contribute to provide scientific evidences into the business application of zinc amino acid complex.
... The increased serum lysozyme activity in the current study might indicate improved innate immune response of the fish. Zinc supplementation has intracellular signaling molecules which play an important role in cell mediated immune functions [52,53]. This indicated that supplementation of zinc can enhance some innate immune response. ...
... Terjadinya peningkatan jumlah limfosit pada kelompok ekstrak ikan gabus dapat dikaitkan dengan adanya kandungan mineral seng pada suplemen ekstrak ikan gabus tersebut yang diketahui dapat mempengaruhi fungsi kekebalan tubuh disamping juga bermanfaat dalam mengembalikan imunitas organisme dengan cara meningkatkan aktivitas enzim katalase dan enzim superoksida dismutase (SOD) dan meningkatkan produksi limfokin sehingga menyebabkan sel limfosit mampu berdiferensiasi dan berproliferasi. 21,22 Selain itu suplemen ekstrak ikan gabus juga mengandung asam amino arginin, dimana arginin merupakan salah satu asam amino esensial yang penggunaannya telah direkomendasikan terutama pada pasien yang mengalami immunodeficieny. Arginin juga dapat memberikan sumbangsih nitrogen yang penting dalam pembentukan oksida nitrat di pembuluh darah dan merupakan komponen penting dalam menghadapi adanya respon terhadap infeksi. ...
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Background: Zinc supplementation in young adults has been found to increase dose-dependent pro-inflammatory cytokines. Increased proinflammatory cytokine has been found in severe sepsis and shock conditions. To determine the effect of zinc administration on normal conditions on pro-inflammatory cytokines compared to sepsis and normal conditions. Methods: A total sample of 40 rats was randomized into four control groups, lipopolysaccharide (LPS), LPS-zinc, and zinc. Placebo normal saline was given intravenously to the control and zinc groups, whereas in the LPS and LPS-zinc groups, intravenous Escherichia coli LPS was given. Blood collection was carried out at the 2nd h after administration to measure zinc levels, and an oral distilled water placebo was given to the control group and LPS, while the LPS-zinc and zinc groups were given zinc supplementation orally for 3 days. At 8, 24, and 72 h, blood was collected to measure tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) levels. At the 72nd h, blood was also taken to measure zinc levels. Examination of TNF-α and IL-6 levels used the enzymelinked immunosorbent assay Sandwich technique, while zinc levels used atomic absorption spectroscopy. Results: The TNF-α level in the zinc group at 72nd h was higher than the control group, while the zinc group’s IL-6 level was higher than the control group at 8th and 24th h. The levels of TNF-α and IL-6 in the zinc group were lower than LPS and LPS-zinc groups. Conclusions: Zinc supplementation under normal conditions increases the cytokines of TNF-α and IL-6. KEY WORDS: Interleukin-6, Normal conditions, Tumor necrosis factor-alpha, Zinc. KEY WORDS: Interleukin-6, Normal conditions, Tumor necrosis factor-alpha, Zinc
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Alzheimer’s disease (AD), the most common type of dementia in the elderly, is a chronic and progressive neurodegenerative disorder with no effective disease-modifying treatments to date. Studies have shown that an imbalance in brain metal ions, such as zinc, copper, and iron, is closely related to the onset and progression of AD. Many efforts have been made to understand metal-related mechanisms and therapeutic strategies for AD. Emerging evidence suggests that interactions of brain metal ions and apolipoprotein E (ApoE), which is the strongest genetic risk factor for late-onset AD, may be one of the mechanisms for neurodegeneration. Here, we summarize the key points regarding how metal ions and ApoE contribute to the pathogenesis of AD. We further describe the interactions between metal ions and ApoE in the brain and propose that their interactions play an important role in neuropathological alterations and cognitive decline in AD.
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Wearable analytical devices represent the future for fast, de-centralized, and human-centered health monitoring. Electrochemistry-based platforms have been highlighted as the role model for future developments amid diverse strategies and transduction technologies. Among the various relevant analytes to be real-time and non-invasively monitored in bodily fluids, we review the latest wearable achievements towards determining essential and toxic metals. On-skin measurements represent an excellent possibility for humankind: real-time monitoring, digital/fast communication with specialists, quick interventions, removing barriers in developing countries. In this review, we discuss the achievements over the last 5 years in non-invasive electrochemical platforms, providing a comprehensive table for quick visualizing the diverse sensing/technological advances. In the final section, challenges and future perspectives about wearables are deeply discussed.
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A 12-week growth trial was conducted to investigate the impacts of dietary zinc on growth performance, whole-body composition, haematological parameters, liver aspartate aminotransferase and alanine transaminase activity and tissue trace mineral contents of soft-shelled turtle (Pelodiscus sinensis). Approximately 4 g of turtles were fed fishmeal-based diets with 35.43, 46.23, 55.38, 66.74, 75.06 and 85.24 mg Zn/kg. Respiratory burst, red blood cells and intestine somatic index enhanced with escalating dietary Zn concentrations up to 55.38 mg/kg and then kept constant beyond this level. Escalating dietary Zn inclusion up to 66.74 mg/kg improved weight gain, survival rate, feed intake, albumin, haemoglobin, liver aspartate aminotransferase and alanine transaminase activity, carapace ratio and crude protein of turtles, beyond which they decreased. Osmolality, hepatosomatic index and crude lipid of turtles firstly declined with elevating dietary zinc levels from 35.43 to 55.38 mg/kg diet and then increased at a higher zinc level. Liver and muscle Zn concentrations enhanced with escalating dietary zinc inclusion, whereas Cu and Fe concentrations reduced. In summary, the optimal dietary zinc requirements for turtles were 61.27, 60.46 and 60.03 mg/kg diet, based on quadratic regression analysis derived from weight gain, aspartate aminotransferase and alanine transaminase activity, respectively.
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Zinc (Zn) is required for proper immune function and host defense. Zn homeostasis is tightly regulated by Zn transporters that coordinate biological processes through Zn mobilization. Zn deficiency is associated with increased susceptibility to bacterial infections, including Streptococcus pneumoniae, the most commonly identified cause of community-acquired pneumonia. Myeloid cells, including macrophages and dendritic cells (DCs), are at the front line of host defense against invading bacterial pathogens in the lung and play a critical role early on in shaping the immune response. Expression of the Zn transporter ZIP8 is rapidly induced following bacterial infection and regulates myeloid cell function in a Zn-dependent manner. To what extent ZIP8 is instrumental in myeloid cell function requires further study. Using a novel, myeloid-specific, Zip8 knockout model, we identified vital roles of ZIP8 in macrophage and DC function upon pneumococcal infection. Administration of S. pneumoniae into the lung resulted in increased inflammation, morbidity, and mortality in Zip8 knockout mice compared with wild-type counterparts. This was associated with increased numbers of myeloid cells, cytokine production, and cell death. In vitro analysis of macrophage and DC function revealed deficits in phagocytosis and increased cytokine production upon bacterial stimulation that was, in part, due to increased NF-κB signaling. Strikingly, alteration of myeloid cell function resulted in an imbalance of Th17/Th2 responses, which is potentially detrimental to host defense. These results (for the first time, to our knowledge) reveal a vital ZIP8- and Zn-mediated axis that alters the lung myeloid cell landscape and the host response against pneumococcus.
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We accessed the effects of dietary Zn on growth, immunity and reproductive performance in female Macrobrachium nipponense. After feeding with a homemade diet containing 21, 50, 81, 136 and 203 mg kg−1 Zn for 60 days, prawns showed a significant increase in weight gain, improved survival, higher hepatosomatic and gonadosomatic indices (p < 0.05) in group 50 and 81 mg kg−1 Zn. Broken‐line analysis indicated that the optimal concentration of dietary zinc was 75.48 mg kg−1. Dietary Zn had drastically increased crude lipid content in body composition (p < 0.05), while moisture, ash and crude protein had no significant difference among groups (p > 0.05). Zn content in hepatopancreas linearly increased along with increases in dietary Zn, while Zn content in muscle and haemolymph had no difference in Zn supplemented groups (p > 0.05). The highest activities of Cu/Zn‐SOD, T‐SOD and CAT in hepatopancreas were in 81 mg kg−1 and 50 mg kg−1 Zn diet, respectively. MDA had the lowest content in 21 to 81 mg kg−1 Zn levels. The highest haemolymph AKP activity was in 81 mg kg−1 Zn diet group, while the highest PO activity was in 136 mg kg−1 Zn diet. Both levels of progesterone and estradiol and gene expression of VG and VGR were highest in 50 to 81 mg kg−1 Zn levels. These results provided evidence that dietary Zn ranging from 50 to 81 mg kg−1 has a positive impact on growth, immunity and reproductive performance of female prawn.
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الخلاصة من خلال الدراسة الحالية والممتدة من 1/5/2019 الى 30/12/2019 فحص 50 عينة دم ومصل شملت (30 عينة لمجموعة الاشخاص المصابين بالليشمانيا الجلدية والاصحاء) و( 20 عينة ذكور للجرذان البالغة السيطرة والاصابة) وتم التأكد من جميع الحالات المصابة من الاطباء الاختصاص بما يخص الاصابة البشرية, اما الحيوانات المختبرية فكانت من خلال الاعراض التشخيصية والسريرية. بينت فحوصات معايير العناصر النزرة في مصل الدم وجود اختلافات معنوية بين المصابين والاصحاء إذ سجل عنصر النحاس لدى المصابين ارتفاعاً معنوياً عند مستوى احتمالية (P≤0.05) بلغت777.01±95.98 جزء بالبليون مقارنة بغير المصابين 667.1±134.10 جزء في البليون وسجل عنصر الحديد انخفاض معنوي لدى مجموعة الاصابة 801.33±87.41 جزء في البليون بالمقارنة مع مجموعة الاصحاء 879.4±98.23 جزء في البليون. أما السيلينيوم فسجلت مجموعة المصابين انخفاض معنوي عند مستوى احتمالية (P≤0.05) حيث بلغ متوسط الاصابة22.38±8.6 جزء في البليون مقارنة مع غير المصابين33.96±4.6 جزء في البليون. ولم يسجل عنصر الزنك فروقات معنوية في مصل الاشخاص المصابين باللشمانيا الجلدية 1.05±0.4 جزء في المليون مقارنة بمجموعة الاشخاص الاصحاء 1.17±0.3 جزء في المليون. أما الجذور الحرة فقد سجلت ارتفاع معنوي في تركيز المالون ثنائي الألديهايد والسوبر اوكسيد ديسموتيزSOD لمجموعة الاشخاص المصابين2.543±0.419 مايكرومول/لتر و 0.128±0.09 بيكوغرام/مل على التوالي بالمقارنة مع مجموعة الاشخاص الاصحاء, وسجل الانزيم المضاد للاكسدة الكلوتاثيون بيروكسيديز ((Gpx والكتاليز CAT انخفاضاً معنويا (P≤0.05) في مجموعة الاصابة إذ بلغ 291.59±149.79 بيكوغرام/مل و3.856±0.76 وحدة/مل على التوالي بالمقارنة مع مجموعة الاشخاص الاصحاء. اما التغايرات في العوامل المناعية للاشخاص فسجل الانترلوكين IL-6 أرتفاع معنوي لدى مجموعة الاصابة بالمقارنة مع مجموعة الاصابة 0.017± 0.035 بيكوغرام/مل. في حين كان هنالك ارتفاع معنوي لعامل التنخر الورمي TNF-α لدى المصابين 0.103±0.201 بيكوغرام/ مل مقارنة مع مجموعة الاشخاص الاصحاء 0.026±0.031) بيكوغرام/مل). ولم يسجل بروتين الالبومين في مصل الاشخاص المصابين بالليشمانيا الجلدية اي تغييرات معنوية في مصل دم (P≥0.05) مقارنة مع الاشخاص الاصحاء 4.918±1.146) بيكوغرام/مل). وأظهرت التغييرات الدموية عند مستوى احتمالية (P≤0.05) في مستويات الهيموغلوبين انخفاض معنوي لمجموعة الاصابة حيث بلغ 13.37±1.77 غم/ديسليز بالمقارنة مع مجموعة الاشخاص الاصحاء 15.82±0.83غم /ديسيليز. أما خلايا الدم البيضاء والخلايا اللمفية و مقراط الدم والصفيحات الدموية فلم تسجل أي فروق معنوية لمجموعة الاصابة بالمقارنة مع مجموعة الاشخاص الاصحاء. وسجلت الخلايا العدلة والحمضة ارتفاع معنوي في مجموعة الاصابة 62.98±9.07 % و6.63±0.62 % على التوالي بالمقارنة مع مجموعة السيطرة 52.99±7.29 % و 5.69±0.88% على التوالي. أما نتائج الفحوصات المختبرية لعينات الدم والمصل للمجموعة التجريبية للجرذان البيض البالغة فلم تسجل العناصر النزرة اي وجود فروق معنوية لمستويات النحاس والزنك مقارنة مع مجموعة السيطرة. أما مستويات الحديد والسيلينيوم فسجلت انخفاضا معنويا في مصل الدم لذكور الجرذان المصابة البالغة 67.95±39.76 8 و 11.897±0.982جزء بالبليون على التوالي مقارنة بمجموعة السيطرة904.28±40.47 و 22.181±4.772 جزء بالبليون على التوالي. اما التغايرات في بعض مضادات الاكسدة والاجهاد التأكسدي في الجرذان البيض المصابة بطفيلي اللشمانيا الجلدية فسجل المالنوالديهايد والسوبر اوكسيد ديسموتيز حصول ارتفاع معنوي (P≤0.05) عند مجموعة الأصابة بالطفيلي حيث سجلت 2.37±0.537 مايكرمول/لتر و0.074±0.130 بيكوغرام/مل على التوالي بالمقارنة مع مجموعة السيطرة 1.46±0.315 مايكرومول/لتر و 0.015±0.016 بيكوغرام/مل على التوالي. في حين سجلت مضادات الاكسدة الانزيمية لمضاد الاكسدة الكلوتاثيون بيروكسديز GPx والكتاليز CAT في مصل الدم لذكور الجرذان المصابة انخفاض معنوي إذ بلغ تركيزه741.08±123.03بيكوغرام/مل و0.268±0.041 وحدة/مل على التوالي بالمقارنة مع مجموعة السيطرة 818.43±83.17 بيكوغرام/مل و0.121±0.049 وحدة/مل على التوالي. أما التغايرات بين العوامل المناعية للحيوانات المختبرية المصابة فسجل الحركي الخلوي (IL-6) وعامل التنخر الورمي TNF-α ارتفاع معنوي عند مستوى احتمالية (P≤0.05) في مصل الدم لذكور الجرذان المصابة بلغ 0.023±0.009و 0.042±0.019 بيكوغرام/ مل بالمقارنة مع مجموعة السيطرة 0.015±0.005 و 0.018±0.008 بيكوغرام/مل على التوالي. اما فحص مستويات بروتين الالبومين في مصل الدم لدى الجرذان البيض المصابة فسجل وجود انخفاض معنوي (P≤0.05) لمجموعة الاصابة بلغت3.489±0.248 بيكوغرام/مل بالمقارنة مع مجموعة السيطرة 3.154±0.335 بيكوغرام/مل. وسجلت نتائج الفحوصات المختبرية للتغييرات الدموية لمجموعة الحيوانات المصابة انخفاض معنوي (P≤0.05) في مستويات الهيموغلوبين ومقراط الدم لمجموعة الاصابة إذ بلغ 13.07±1.52غم /ديسيليز و 36.48±3.725% بالمقارنة مع مجموعة السيطرة 14.71±1.49 غم /ديسليز و%42.50±3.496 على التوالي. أما العدد الكلي لخلايا الدم البيضاء والخلايا العدلة والصفيحات الدموية فلم تسجل أي فروق معنوية لمجموعة الاصابة مقارنة مع مجموعة السيطرة . في حين سجلت الخلايا اللمفية والحمضات ارتفاع معنوي لدى مجموعة الاصابة وكان متوسط التركيز 75.64±5.52 % و 4.13±0.823 % على التوالي بالمقارنة مع مجموعة السيطرة. اظهرت فحوصات صور المجهر الالكتروني الماسح للانبعاثات الحقلية Fe-SEM للجلد والشعر جرذ لمجموعة السيطرة عدم وجود اي تغيرات مرضية غير طبيعية. في حين اوضحت مجموعة الاصابة بداية ظهور التقرحات والارتفاعات الجلدية الناجمة عن الاصابة وبأقطار مختلفة مع ملاحظة وجود تشققات جلدية مقارنةً بالجلد الطبيعي, مع تأثر كبير للشعرة و تنخر و وجود حبيبات ملوثة بالطفيلي او انفجار البلاعم الحاوية على الطفيلي macrophage وحصول تقصف وتحطم او تكسر الكيراتين مع انسلاخات وظهور سطح غير منتظم للشعرة. كذلك اظهر فحص نسيج الكبد لمجموعة السيطرة متن كبدي سليم ذي سطح منتظم للخلايا الكبدية خالي من اي اصابة, وأظهر الفحص الشكل الهندسي النسيجي للفصيصات الكبدية سليمة ومنتظمة والورم الحبيبي granulomaبالمقارنة مع المجموعة المصابة. أما مجموعة الاصابة فقد اظهرت نتائج الفحص سطح غير منتظم لمتن الكبد المغلفة لفصوص الكبد, وفقدان وظائف النسيج الضام الكثيف Dense connective tissue للكبسولة وتشوه الحواف للفص الكبدي Border irregular وظهور تلييفات fibrosis , وتنكس فجوي للخلايا vacular degeneration, وورم حبيبي نتيجة الاصابة بالطفيلي Granuloma مع ملاحظة غياب الترتيب الشعاعي لنسيج الكبد. وحصول تنخر Necrosis, تمزق الخلايا Cell Disruption, توسع الجيبانيات sinusoid dilation, وملاحظة الموت الخلوي المبرمج للخلايا Apoptosis, و خلايا بلازما Plasma cell. أما نسيج الطحال لمجموعة السيطرة فقد أظهر التركيب الطبيعي للطحال. أما مجموعة الاصابة سجلت ظهور سطح غير منتظم ومرتفع اللب الابيض, مع اللب الاحمر مع كثرة الكريات الحمر ووجود البثرات والخلايا لمفاوية Lymphocyte و البلعميات macrophage مع خلايا بلازمية Plasma cell , وغياب الشكل الهندسي للشريان المركزي central artery, مع وضوح الموت المبرمج Programmed death, وتقرحات Ulcer, وتضخم الخلايا Cell enlargement وخاصة الخلايا اللمفاوية Lymphocyte , اما اقطار الخلايا فكانت اكبر نتيجة التضخم الناجم عن الاصابة.
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Zinc and Zinc Deficiency with emphasis on the immune system and cancer
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Zinc is an essential heavy metal that plays an important role in nucleic acid metabolism, cell replication, and tissue growth and repair, and its deficiency is associated with a variety of disorders. Zinc directly affects the activity of several signaling molecules and of transcription factors that have a zinc-binding motif. However, it has not been clearly shown whether zinc itself acts as an intracellular signaling molecule like calcium. Several groups have presented evidence that zinc does indeed act as an intracellular signaling molecule, converting extracellular stimuli to intracellular signals and controlling various cell functions. This chapter summarizes our current understanding of zinc signaling, especially with regard to Zinc wave and the role of zinc signaling in Fc receptors and T- and B-cell antigen receptors, and discusses how these processes contribute to cytokine production.
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Zinc is an essential element in The development and function of the immune system. This article reviews some of the newest data on its role in immunity.
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Thymus endocrinology is characterized by the action of various hormones on the thymus endocrine milieu consisting of thymocytes, thymic epithelial cells and thymic stromal cells. Extrathymic hormonal influences include pituitary-derived hormones, such as prolactin and indirectly by ACTH via hydrocortisone from the adrenal, by thyroid-stimulating hormone (TSH) via thyroid hormones from the thyroid, and by LH and RH via sex steroids from gonads and adrenal. In addition, the thymus produces several putative thymic hormones: thymosin alpha 1, thymulin and thymopoietin, which have been reported to circulate and to act on both prothymocytes and mature T-cells in the periphery thus maintaining their commitment to the T-cell system and its functions. These endocrine influences decline with age and are associated with "thymic menopause" and cellular immune senescence contributing to the development of diseases in the aged. The intrathymic environment is characterized by a complex network of paracrine and autocrine endocrine signals involving both interleukins and thymic peptides. Thymic epithelial cells respond to IL-1 with proliferation and secretion of IL6 and GM-CSF. They similarly respond to cellular interactions with the production of IL1. Thymic epithelial cells also secrete thymic hormones, as exemplified by the zinc-thymulin complex, under stimulation with IL1 and other hormonal influences. Thymic stromal cells contribute, at minimum, IL1. These various interleukin and thymic hormone influences can be envisioned to operate in a synergistic interactive network to carry the evolving T-cell through its stepwise development to a mature T-cell.(ABSTRACT TRUNCATED AT 250 WORDS)
Article
A preliminary trial of oral zinc supplementation was conducted in twenty-four patients with chronic, refractory rheumatoid arthritis. Zinc sulphate (220 mg three times daily) or placebo capsules of identical appearance were added to pre-existing therapy for 12 wk. This double-blind trial was followed by an open 12-wk period when all subjects took zinc. During the double-blind phase, zinc-treated patients fared better than controls with regard to joint swelling, morning stiffness, walking time, and the patient's own impression of overall disease activity. The indices and joint tenderness also improved with zinc treatment in both groups of subjects during the second 12-wk period. These encouraging results indicate that oral zinc sulphate deserves futher study in patients with active rheumatoid arthritis.
Article
Zinic ions rapidly inhibit virus production in HeLa cells infected with human rhinovirus type 1A and lead to the accumulation of human rhinovirus type 1A precursor polypeptides. The degree to which cleavage of these precursors is inhibited is directly dependent on the quantity of cell-associated zinc. Proteolysis resumes after the removal of zinc-containing medium, and the accumulated viral precursors are cleaved predominantly to stable virus polypeptides. The precursors stabilized at the lowest zinc levels are those that contain capsid protein sequences. Furthermore, added zinc is bound to human rhinovirus type 1A capsids and prevents them from forming crystals. Zinc-resistant mutants display antigenic alterations in coat proteins. These results suggest that zinc complexes with rhinovirus coat proteins and alters them so that they cannot function as substrates for proteases or as reactants in the assembly of the virus particles.
Article
Subpopulations of human peripheral blood leucocytes were isolated by nylon filtration or E-rosette separation and tested for functional activity. As shown previously, zinc ions induce DNA synthesis in unfractionated lymphocyte cultures. E-rosette-forming cells (E-RFC), obtained either by nylon wool filtration or E-rosette separation, responded well to PHA but showed only low levels of proliferative reactivity to zinc and Con A. These dminished responses could be completely restored by the addition of small numbers of autologous, mitomycin-treated monocytes; further experiments suggested that a monocyte-derived soluble factor can substitute for monocytes in this function. B lymphocyte-enriched cell populations, containing less than 1% E-RFC, did not respond to zinc and showed only marginal reactivity to PHA and Con A.
Article
In this paper the importance of zinc in determining normal and perturbed immune functions is reassessed. The human zinc deficiency is due to rare genetic abnormalities, acquired pathologic conditions and, very often dietary insufficiency. A response to acute stress after a bacterial infection causes profound effects upon serum zinc fluctuations. Zinc is an absolute requirement for lymphocyte transformation. Zinc could be operating at several different levels in influencing lymphocyte mitogenic response. In human zinc deficiency disease and in induced deficiency states in animals thymic hypoplasia and deficient T lymphocyte-mediated functions are the most consistent findings, which can be restored by zinc therapy. The available informations about the relationship between zinc immunodeficiency and cancer are not complete enough to permit the conclusion that the presence of cancer is, in itself, associated with a depression of serum zinc, in spite of the presence of depressed immune parameters. (Dr. J.Sugar - Budapest - Hungary)
Article
It is becoming increasingly evident that zinc ions as an integral part of tissues and biologic fluids are one of many homeostatic mechanisms regulating the reactivity of tissues and cells. Various aspects of the role of zinc in preserving the integrity of the cells and tissues were reviewed by the author recently. In this report, he concentrates on the effect of zinc on cells as documented in the literature or by his experiments aimed at the analysis of the mechanisms of the mode of action of this cation at the cellular level. Finally he points to some perspectives of this field of research and discusses briefly a few clinical implications of the data presented.
Article
Radioiodinated zinc transferrin has been found to interact with human lymphocytes in a manner characterized by rapid binding, saturability, reversibility, and specificity. Each lymphocyte can bind a maximum of approximately 61,000 molecules of zinc transferrin with an association constant of 4 x 10/sup 7/ M/sup -1/. Binding is strongly inhibited by cyanide and fluoride and only moderately inhibited by sulfhydryl reagents.
Article
The therapeutic effect of orally administered zinc was evaluated in an adult woman with acrodermatitis enteropathica. When she was off therapy and in clinical relapse the plasma zinc concentration (10 mug per 100 ml), serum alkaline phosphatase (3 1U per liter) and urine zinc excretion rate (39 mug per 24 hours) were extremely low. Di-iodohydroxyquin therapy was accompanied by a modest increase in plasma zinc concentrations. Oral zinc sulfate (220 mg three times a day or 50 mg twice a day) resulted in rapid and complete clinical remission, and in a return of plasma zinc, serum alkaline phosphatase and urinary zinc excretion to normal. These data are compatible with a severe zinc deficiency state and indicate that the inherited defect in this disease is either in or closely related to zinc metabolism. The beneficial effects of zinc therapy in this patient provide further confirmation of the efficacy of oral zinc in the treatment of acrodermatitis enteropathica.
Article
In serum-free cultures of phytohemagglutinin-stimulated human lymphocytes, iron transferrin causes enhanced uptake of both tritiated thymidine and tritiated uridine over that seen with only phytohemagglutinin. This effect is specific for the iron transferrin complex, no enhancement produced by either free iron(III) or apotransferrin. Iron bound to transferrin is quantitatively taken up by stimulated lymphocyte cultures, while under similar conditions only 10% of transferrin-bound zinc is incorporated. The relative specificity of action of iron and zinc on nucleic acid synthesis is discussed.
Article
Human serum proteins of blood donors and dialysis patients were separated by means of gel filtration chromatography. The resulting fractions were analyzed for copper and zinc. Separation resulted in 3 zinc peaks with a molecular weight of about 700,000, 300,000, and 75,000 Dalton, with alpha 2-macroglobulin co-eluting in the first and albumin co-eluting in the third zinc peak. The zinc protein(s) of the second peak remained unidentified. The three peaks contained, in succession, 0.72 +/- 0.30 mumol/L (4.8 +/- 1.6%), 1.26 +/- 0.37 mumol/L (8.5 +/- 1.7/1000) and 12.8 +/- 2.1 mumol/L (86.8 +/- 2.8%) of total zinc in the case of blood donors, and 1.19 +/- 1.05 mumol/L (9.2 +/- 7.2%), 0.97 +/- 0.22 mumol/L (8.0 +/- 2.6%), and 10.4 +/- 1.66 mumol/L (82.7 +/- 6.7%) in the case of dialysis patients. Separation followed by copper analysis resulted in the three peaks, as well, with a molecular weight of about 750,000, 140,000, and 75,000 dalton. The copper protein of the first peak remained unidentified, while coeruloplasmin co-eluted in the second and albumin in the third peak. The three peaks contained, in succession, 0.4 +/- 0.16 mumol/L (2.3 +/- 0.95%), 14.6 +/- 0.7 mumol/L (83.9 +/- 4.1%), and 2.4 +/- 0.6 mumol/L (13.7 +/- 3.5%) of total copper in the case of blood donors, and 0.5 +/- 0.73 mumol/L (2.2 +/- 3.2%), 19.5 +/- 1.1 mumol/L (90.5 +/- 4.9%), and 1.6 +/- 0.66 mumol/L (7.3 +/- 3.0/1000) in the case of dialysis patients. Limitation of the method is shown regarding separation of major from minor proteins and albumin from transferrin.
Article
Zinc is a very important element in the reproductive cycle of species. In humans, it is necessary for the formation and maturation of spermatozoa, for ovulation, and for fertilization. During pregnancy, zinc deficiency causes a number of anomalies: spontaneous abortion, pregnancy-related toxemia, extended pregnancy or prematurity, malformations, and retarded growth. Delivery is adversely affected by deficiency. These different effects of zinc can be explained by its multiple action on the metabolism of androgen hormones, estrogen and progesterone, together with the prostaglandins. Nuclear receptors for steroids are all zinc finger proteins. Zinc supplementation has already proven beneficial in male sterility and in reducing complications during pregnancy. However, it would be worth conducting larger-scale trials to confirm these beneficial effects.
Article
In the past five years there has been a great expansion in our knowledge of the role of zinc in the structure and function of proteins. Not only is zinc required for essential catalytic functions in enzymes (more than 300 are known at present), but also it stabilizes and even induces the folding of protein subdomains. The latter functions have been most dramatically illustrated by the discovery of the essential role of zinc in the folding of the DNA-binding domains of eukaryotic transcription factors, including the zinc finger transcription factors, the large family of hormone receptor proteins, and the zinc cluster transcription factors from yeasts. Similar functions are highly probable for the zinc found in the RNA polymerases and the zinc-containing accessory proteins involved in nucleic acid replication. The rapid increase in the number and nature of the proteins in which zinc functions is not unexpected since zinc is the second most abundant trace metal found in eukaryotic organisms, second only to iron. If one subtracts the amount of iron found in hemoglobin, zinc becomes the most abundant trace metal found in the human body.
Article
Thymic epithelial cells (TEC) are known to secrete thymic hormones that influence maturation of T lymphocytes. One of these peptides, thymulin, requires zinc in an equimolar ratio for biological activity. A previous study [Cousins, R. J. & Leinart, A. S. (1988) FASEB J. 2, 2884-2890] showed that interleukin 1 (IL-1) in vivo stimulates zinc uptake by the thymus. Both the alpha and beta forms of IL-1, which stimulate proliferation of human TEC, also stimulate their uptake of zinc in vitro, and this latter stimulation is both dependent and independent of proliferation. Zinc induces zinc accumulation without proliferation. Two other stimulants of proliferation, bovine pituitary extract and epidermal growth factor, stimulate zinc uptake by TEC, but only in a manner dependent on proliferation. Utilizing in situ hybridization, we show that the IL-1 alpha and beta forms and zinc induce metallothionein mRNA expression TEC. Metallothionein is thought to be involved in the transfer of zinc to thymulin. IL-1 was shown to stimulate the secretion of thymulin as measured both by its ability to stimulate induction of IL-2 receptor-positive lymphocytes from human peripheral blood lymphocytes and by the azathioprine-sensitive rosette assay. In addition, the zinc-thymulin complex in the presence, but not absence, of IL-1 stimulates nuclear protein kinase C in isolated lymphocyte nuclei. IL-1 apparently regulates the synthesis or secretion and delivery of zinc-thymulin complex to the T-lymphocyte system.
Article
To determine whether specific nutrient abnormalities occur in earlier stages of HIV-1 infection, thereby preceding the marked wasting and malnutrition that accompany later stages of the infection. A longitudinal investigation to determine biological, psychological and social factors thought to influence the progression and outcome of HIV-1 infection. Nutritional status was assessed using biochemical measurement of nutrient levels, dietary history, anthropometry and clinical examination for the signs and symptoms of nutritional deficiency or excess. The study was performed on an outpatient basis at the University of Miami School of Medicine. One hundred homosexual men, aged between 20 and 55 years, who were asymptomatic other than persistent generalized lymphadenopathy (Centers for Disease Control stage III) and 42 age-matched homosexual men demonstrated to be free of HIV-1 infection at two 6-month intervals. Biochemical measurement of nutrient status, dietary history, anthropometry, clinical signs or symptoms of nutritional excess or deficiency were obtained for all participants. Despite few differences in mean blood levels of specific nutrients, prevalence of specific nutrient abnormalities was widespread among HIV-1-infected subjects, compared with non-infected male homosexual controls. Overtly and marginally low blood levels of vitamins A (18%), E (27%), riboflavin (26%), B6 (53%), and B12 (23%), together with copper (74%) and zinc (50%) were documented in HIV-1-seropositive subjects. With the exception of riboflavin, zinc, and copper, a similar prevalence of abnormalities among HIV-1-seronegative controls was not observed. Specific nutrient abnormalities occur with relative frequency in asymptomatic HIV-1 infection and may contribute to the rate and form of HIV-1 disease progression.
Article
Staphylococcal enterotoxins bind with high affinity to class II major histocompatibility complex proteins and subsequently stimulate large numbers of T cells via the V beta portion of the T-cell receptor. Binding of enterotoxin A and enterotoxin E to HLA-DR was completely abolished by low levels of EDTA, whereas binding of toxic shock toxin was unaffected. Addition of Zn2+ to as little as 2 microM excess over EDTA completely reconstituted binding, but Ca2+, Mg2+, Cu2+, Fe2+, and Mn2+ had no effect. The dissociation constant (Kd) of 65Zn2+ binding to a single site on purified enterotoxin A was 2 microM, and addition of purified HLA-DR1 did not alter the Kd, indicating that the binding site was exclusive to enterotoxin A. In the presence of saturating levels of zinc the Kd for enterotoxin A binding to purified HLA-DR1 was 25 nM. Thus, zinc binding is an essential first step in the formation of the major histocompatibility complex binding domain of at least two bacterial superantigens. Given the measured Kd of zinc binding to enterotoxin A, serum levels of free zinc (0.2-1.0 microM) may well regulate the toxic sequelae by these two superantigens.
Article
We investigated the zinc concentration in blood and the effect of zinc supplementation in 11 male outpatients seropositive for human immunodeficiency virus at stage 5 according to the Walter Reed classification. Zinc concentration was measured in serum, platelets, mononuclear and polymorphonuclear cells, and erythrocytes. There was a significant increase in serum zinc concentration after zinc administration, but the zinc level in blood cells remained unchanged. All patients showed a progressive gain in body weight and a slight elevation in levels of CD4+ cells. No adverse side-effects were noticed.
Article
Cytokines are often thought of as short range, short half-life molecules. This view may now be challenged by recent findings that indicate that alpha 2-macroglobulin and antibodies to cytokines may alter cytokine kinetics in vivo. alpha 2-Macroglobulin, one of the major proteins in serum, can bind a wide range of physiologically important molecules. As Keith James reviews here, the interaction between alpha 2-macroglobulin and a number of cytokines has recently come under scrutiny, revealing a new and potentially important mechanism for the modulation of cytokine activity, while in the following paper a modulatory role for anti-cytokine antibodies is considered.
Article
There is some evidence to suggest that microbial growth inhibition may occur in chronic abscesses. A substance perhaps responsible for this phenomenon is calprotectin, a neutrophil cytoplasmic protein that inhibits microbial growth and that belongs to a class of proteins often having specific binding sites for zinc. In the present study, the suppressive effects of either human or mouse neutrophillysates on Candida albicans growth were found to be completely reversed by micromolar quantities of zinc but not by iron or other trace elements. Similarly, supernatants of exudates from experimental abscesses in mice or from clinical specimens of abscesses in humans markedly inhibited the proliferation of C. albicans, and this effect was also completely reversed by zinc. A protein complex characteristic of calprotectin was identified in the abscess fluids. Preparations of the neutrophil growth-inhibiting protein, containing predominantly calprotectin, were shown to have zinc-binding activity by a dialysis technique. These findings suggest that the major mechanism of C. albicans growth inhibition by abscess fluids is through competition for zinc by a cytoplasmic protein apparently released from dying neutrophils.
Article
The addition of copper and zinc salts to human peripheral blood leukocytes cultured in complete medium containing endotoxin and fetal calf serum stimulated tumor necrosis factor (TNF) secretion in a concentration-dependent manner. The secretion of interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) was inhibited by copper under the same culture conditions, while zinc stimulated IL-1 beta secretion in a concentration-dependent manner and had no effect on leukocyte IL-6 release. Both copper and zinc induced increases in TNF mRNA (54 and 14%, respectively) when compared to cells cultured in complete medium alone. In serum-free, low endotoxin medium (less than 6 pg/ml), both copper and zinc failed to stimulate either TNF or IL-1 beta secretion. Under the same conditions the addition of lipopolysaccharide (LPS), at concentrations above 0.01 micrograms/ml, induced a concentration-dependent release of both cytokines. When either copper or zinc were combined with 0.01 micrograms/ml LPS, a synergistic stimulation of TNF secretion resulted. IL-1 beta secretion, unlike TNF, was not synergistically stimulated by combining metals and LPS in serum-free medium. Combining copper and zinc with inhibitors of TNF secretion, transforming growth factor beta, prostaglandin E2, and plasma alpha-globulins, resulted in a reduction of the suppressive effects of each of these agents. This study suggests that the trace metals copper and zinc may play important and possibly distinct roles in regulating leukocyte secretion of TNF, IL-1 beta, and IL-6.
Article
The effects of a single nutrient deficiency on immune function is now most extensively characterized using the dietary zinc deficient murine model. Deficiencies in zinc have rapid adverse effects on host defenses of humans and rodents. This impaired defense seems to be, in part, the result of a reduction in number of lymphocytes available for surveillance since residual lymphocytes are able to carry out many normal functions. In vitro, the lymphocytes were able to proliferate at a normal rate as well as produce antibodies or interleukin 2 in response to mitogens or antigens even when cultured in autologous serum to reduce the possibility of restoration of zinc deficient functions. Conversely, mononuclear phagocytes (MNP) from deficient mice had a significantly reduced capacity to associate with and kill the parasite Trypanosoma cruzi (T. cruzi) which causes Chaga's disease. Moreover, indicating the specificity of the deficient function, a short incubation of ZnCl2 but not other metals completely restored the capacity of MNP from deficient mice to take up and kill T. cruzi. Dependency on H2O2 production by the MNP's oxygen burst for killing of T. cruzi.suggested that MNP from zinc deficient mice might produce smaller amounts of H2O2. The possibility that zinc might play an integral role in the oxygen burst seemed evident from the ability of zinc to quickly restore the killing capacity of MNP from the zinc deficient mice. Further, the renewed interest in the role of metals in the production of highly reactive oxidants in biological systems prompted a literature search to identify enzymes and/or reactions known to be involved in the generation of oxygen radicals or toxic oxygen metabolites that might be zinc dependent. The literature review provided herein indicates many possible roles for zinc in the generation of toxic oxygen species. The data indicated that normal levels of H2O2 are produced by MNP from zinc deficient mice. The amount of H2O2/mg macrophage protein is normal in response to phorbol or opsonized zymosan but reduced in response to direct stimulation by T. cruzi. However, the reduced H2O2 production by T. cruzi-stimulated zinc deficient MNP was due to reduced stimulation as a result of fewer T. cruzi associated with the MNP. Thus, H2O2 levels/parasite were the same as zinc adequate controls. Yet, this does not preclude the possibility that reduced killing of T. cruzi by MNP from zinc deficient mice may be due to a function for zinc in the actual killing process or in the production of some other agent important in the killing of T. cruzi.
Article
Zn deficiency can have marked effects on virtually all components of the immune system. That these effects can be functionally significant is demonstrated by the increased susceptibility of Zn-deficient animals to a number of bacterial, viral, and parasitic challenges. In addition, strong epidemiological data support the belief that Zn deficiency is a major factor underlying immune dysfunction in select human populations. Despite recognition of the importance of Zn in the ontogeny and functioning of the immune system, the biochemical lesions underlying the effects of Zn deficiency on immune responsivity have not been well characterized. Future efforts to delineate the effects of Zn on the production, release, and action of cytokines will likely produce significant advances in our understanding of the influence of this element on the immune system. The recent observation that Zn may be critical for the activity and binding of protein kinase C in lymphocyte membranes suggests that another fruitful area of research will involve examination of the influence of Zn deficiency on lymphocyte membrane structure and function. Finally, the recent recognition that Zn may be a critical factor in the activation/inactivation of immunoregulatory genes provides us with yet another avenue of research.
Article
Protein kinase C was measured in the cytoskeletal fraction of lymphocytes, platelets and HL60 cells, by specific binding of [3H]phorbol dibutyrate and by immunoblotting with antibody to a consensus sequence in the regulatory domain of alpha-, beta- and gamma-isozymes of protein kinase C. Treatment of cells for 40 min with a combination of zinc (2-50 microM), zinc ionophore pyrithione and unlabelled phorbol dibutyrate (200 nM) caused up to a ten-fold increase in cytoskeletal protein kinase C and a corresponding decrease in other cellular compartments. Omission of any of the reagents resulted in much less or no translocation. These effects were inhibited by 1,10-phenanthroline, which chelates zinc, and were not seen with calcium. Increase in cytoskeletal protein kinase C persisted for several hours and appeared to involve attachment of the enzyme to actin microfilaments. We propose that zinc, like calcium, regulates the distribution of PKC in cells. However, unlike calcium which controls the binding of PKC to the lipid component on cell membranes, zinc controls the distribution of PKC to membrane cytoskeleton, possibly actin.
Article
Although consequences of zinc deficiency have been recognized for many years, it is only recently that attention has been directed to the potential consequences of excessive zinc intake. This is a review of the literature on manifestations of toxicity at several levels of zinc intake. Zinc is considered to be relatively nontoxic, particularly if taken orally. However, manifestations of overt toxicity symptoms (nausea, vomiting, epigastric pain, lethargy, and fatigue) will occur with extremely high zinc intakes. At low intakes, but at amounts well in excess of the Recommended Dietary Allowance (RDA) (100-300 mg Zn/d vs an RDA of 15 mg Zn/d), evidence of induced copper deficiency with attendant symptoms of anemia and neutropenia, as well as impaired immune function and adverse effects on the ratio of low-density-lipoprotein to high-density-lipoprotein (LDL/HDL) cholesterol have been reported. Even lower levels of zinc supplementation, closer in amount to the RDA, have been suggested to interfere with the utilization of copper and iron and to adversely affect HDL cholesterol concentrations. Individuals using zinc supplements should be aware of the possible complications attendant to their use.
Article
The mechanism whereby zinc regulates the in vitro antibody synthesis of human peripheral blood mononuclear cells was investigated. In a serum-free culture, zinc inhibited the pokeweed mitogen (PWM)-induced generation of immunoglobulin secreting cells (ISC) through an apparent non-specific augmentation of T-cells, which included CD4 and CD8 cells, as well as both CD8-Leu8+ and CD8-Leu8- cells. It was noted that CD4 cells were more stimulated than CD8 cells, and that CD8-Leu8- cells were more stimulated than CD8 Leu8+ cells. CD8-Leu8- cells inhibited the development of ISC. These findings indicate that, although zinc stimulates all T-cells, the relative potency of zinc differs among T-cell subsets; helper inducer T-cells appear to be most strongly stimulated.
Article
Zinc performs a number of unique functions in immunology, which distinguish it from all other trace elements. This special role is based upon its properties as a catalyst of a larger number of enzyme-controlled metabolic processes. Zinc supports, it even enhances, humoral and cell-mediated immunity by facilitating proliferative reactions to stimulus by different mitogens. This is as a result of its acting, above all, on the cell as co-factor for 24 presently known, important enzymes, by exercising a biocatalytic influence and regulatory (in the sense of protective) function. A long-term reduction in food intake, especially extended parenteral feeding, without taking special account of trace elements, leads for all of them, but especially for zinc, to a depletion of body reserves. The latter results in immunological changes that are at first sub-clinical and scarcely recognizable, but which, over the course of time, can lead to life-threatening infections. Cell-mediated immunity, antibody reactions and antibody affinity, complement system and phagocyte activity are perceptibly diminished. The zinc concentration in the blood has an essential influence on the extent and consequences of immunological deficiency.