Zinc supplementation attenuates cardiac remodelling after experimental myocardial infarction.

PMID: 

Cell Physiol Biochem. 2018 ;50(1):353-362. Epub 2018 Oct 4. PMID: 30286450

Abstract Title: 

Zinc Supplementation Attenuates Cardiac Remodeling After Experimental Myocardial Infarction.

Abstract: 

BACKGROUND/AIMS: The objective of our study was to evaluate the effects of zinc supplementation on cardiac remodeling following acute myocardial infarction in rats.METHODS: Animals were subdivided into 4 groups and observed for 3 months: 1) Sham Control; 2) Sham Zinc: Sham animals receiving zinc supplementation; 3) Infarction Control; 4) Infarction Zinc. After the followup period, we studied hypertrophy and ventricular geometry, functional alterations in vivo and in vitro, changes related to collagen, oxidative stress, and inflammation, assessed by echocardiogram, isolated heart study, western blot, flow cytometer, morphometry, and spectrophotometry.RESULTS: Infarction induced a significant worsening of the functional variables. On the other hand, zinc attenuated both systolic and diastolic cardiac dysfunction induced by infarction. Considering the infarct size, there was no difference between the groups. Catalase and superoxide dismutase decreased in infarcted animals, and zinc increased its activity. We found higher expression of collagens I and III in infarcted animals, but there was no effect of zinc supplementation. Likewise, infarcted animals had higher levels of IL-10, but without zinc interference. Nrf-2 values were not different among the groups. Infarction increased the amount of Treg cells in the spleen as well as the amount of total lymphocytes. Zinc increased the amount of CD4+ in infarcted animals, but we did not observe effects in relation to Treg cells.CONCLUSION: zinc attenuates cardiac remodeling after infarction in rats; this effect is associated with modulation of antioxidant enzymes, but without the involvement of collagens I and III, Nrf-2, IL-10, and Treg cells.

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Inflammatory response under zinc deficiency is exacerbated by dysfunction of the T helper type 2 lymphocyte–M2 macrophage pathway.

PMID: 

Immunology. 2019 04 ;156(4):356-372. Epub 2019 Jan 21. PMID: 30552817

Abstract Title: 

Inflammatory response under zinc deficiency is exacerbated by dysfunction of the T helper type 2 lymphocyte-M2 macrophage pathway.

Abstract: 

Nutritional zinc deficiency leads to immune dysfunction and aggravates inflammation. However, the underlying mechanism remains unknown. In this study, the relationship between macrophage subtypes (M1 and M2) and helper T lymphocytes (Th1 and Th2) was investigated using the spleen from rats fed zinc-deficient or standard diet. In experiment I, 5-week-old male Sprague-Dawley rats were fed a zinc-deficient diet (without zinc additives) or a standard diet (containing 0·01% zinc) for 6 weeks. In experiment II, the rats were divided into four groups: one group was fed a standard diet for 6 weeks; two groups were fed zinc-deficient diets and were injected three times a week with either saline or interleukin-4 (IL-4) (zinc-deficient/IL-4 i.p.); a fourth group (zinc-deficient/standard) was fed a zinc-deficient diet for 6 weeks followed by a standard diet for 4 weeks. In experiment I; GATA-binding protein 3 (GATA-3) protein level, M2 macrophage, CD3 CD8cells, and IL-4/IL-13-positive cells significantly decreased in the spleens of the zinc-deficient group. Additionally, IL-1β and macrophage inflammatory protein-1α (MIP-1α) mRNA levels significantly increased in the splenic macrophages of the zinc-deficient group. In experiment II; M2 macrophages, CD3 CD8cells, IL-4/IL-13-positive cells, and GATA-3 protein levels significantly increased in the spleens of the zinc-deficient/IL-4 i.p. and zinc-deficient/standard groups. Furthermore, IL-1β and MIP-1α mRNA levels decreased in the splenic macrophages of the zinc-deficient/IL-4 i.p. and zinc-deficient/standard groups. Zinc deficiency-induced aggravated inflammation is related to Th2 lymphocytes and followed by the association with loss of GATA-3, IL-4 and anti-inflammatory M2 macrophages. Importantly, IL-4 injection or zinc supplementation can reverse the effects of zinc deficiency on immune function.

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The role of zinc and zinc homeostasis in macrophage function.

PMID: 

J Immunol Res. 2018 ;2018:6872621. Epub 2018 Dec 6. PMID: 30622979

Abstract Title: 

The Role of Zinc and Zinc Homeostasis in Macrophage Function.

Abstract: 

Zinc has long been recognized as an essential trace element, playing roles in the growth and development of all living organisms. In recent decades, zinc homeostasis was also found to be important for the innate immune system, especially for maintaining the function of macrophages. It is now generally accepted that dysregulated zinc homeostasis in macrophages causes impaired phagocytosis and an abnormal inflammatory response. However, many questions remain with respect to the mechanisms that underlie these processes, particularly at the cellular and molecular levels. Here, we review our current understanding of the roles that zinc and zinc transporters play in regulating macrophage function.

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Zinc inhibited LPS-induced inflammatory responses by upregulating A20 expression in microglia BV2 cells.

PMID: 

J Affect Disord. 2019 Apr 15 ;249:136-142. Epub 2019 Feb 12. PMID: 30772740

Abstract Title: 

Zinc inhibited LPS-induced inflammatory responses by upregulating A20 expression in microglia BV2 cells.

Abstract: 

BACKGROUND: Our previous studies have proved that zinc supplement effectively alleviate depression symptoms in mice, but the mechanisms are still uncertain. Neuroinflammation is considered as an important aspect in pathogenesis of depression. To elucidate the role of zinc on neuroinflammation, in this study, we investigated effects of zinc on lipopolysaccharide (LPS)-induced inflammation in BV2 microglia cells, a kind of innate immune cells in central nervous system.METHODS: BV2 cells were treated by 100 ng/ml LPS to induce inflammatory responses and the effects of zinc sulfate (ZnSO) addition on LPS-induced inflammation were observed. Besides, through culturing HT-22 hippocampus cells by using medium transferred from zinc-intervened BV2 cells, the protective roles of zinc on hippocampus cells were identified.RESULTS: LPS treatment up-regulated expressions of CD11b, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX2), tumor necrosis factorα (TNFα) and interleukin-6 (IL-6) and level of reactive oxygen species (ROS). Meaningfully, zinc was capable of blocking ROS generation and reducing expressions of the above inflammatory cytokines at both 10 μM and 30 μM. In addition, it was proved that zinc intervention to BV2 cells could increase the viabilities of hippocampal HT-22 cells cultured by medium of BV2 cells. Furthermore, the zinc-finger protein A20, an anti-inflammation factor, was increased by zinc supplement, while levels of p65, p-IκB and p-p65 were significantly decreased.LIMITATIONS: More compelling proofs were needed to ensure roles of A20 in anti-inflammatory effects of zinc.CONCLUSIONS: The present results suggested that zinc inhibits inflammatory responses mediated by microglia cells via upregulation of zinc-finger A20. It was proposed that this anti-inflammatory action might be underlying mechanism of previously observed anti-depressive effects of zinc.

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Fever duration and length of hospital stay were longer in children with zinc deficiency compared to those who had normal levels.

PMID: 

Pediatr Rep. 2019 Feb 26 ;11(1):7386. Epub 2019 Feb 26. PMID: 30838119

Abstract Title: 

Zinc deficiency in children with Dengue viral infection.

Abstract: 

Zinc deficiency is highly prevalent in low-income countries, with dramatic consequences to child health, in particular by impairing the immune system resulting in infection. This cross-sectional study aimed to determine the prevalence of zinc deficiency in Thai children who were admitted to hospital with a diagnosis of the dengue viral infection. Standard cut-off values according to age, sex, time of blood collection, and fasting status were used to define zinc levels. 32 patients were included in the analysis: The mean age was 7.3 years, of whom 56.3% were males. 11 (34.4%) patients were diagnosed with dengue hemorrhagic fever and the remaining had dengue fever. The prevalence of zinc deficiency was 46.7%, with boys having a higher risk of zinc deficiency than girls (OR=7.3: 95%CI: 1.5-36.6). Fever duration and length of hospital stay were longer in children with zinc deficiency compared to those who had normal levels, albeit without a significant difference. The results of this study provide the rationale for larger studies that will better elucidate the relationship between zinc levels and the clinical outcomes of dengue disease.

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Zinc nutrition and inflammation in the aging retina.

PMID: 

Mol Nutr Food Res. 2019 08 ;63(15):e1801049. Epub 2019 Jun 27. PMID: 31148351

Abstract Title: 

Zinc Nutrition and Inflammation in the Aging Retina.

Abstract: 

Zinc is an essential nutrient for human health. It plays key roles in maintaining protein structure and stability, serves as catalytic factor for many enzymes, and regulates diverse fundamental cellular processes. Zinc is important in affecting signal transduction and, in particular, in the development and integrity of the immune system, where it affects both innate and adaptive immune responses. The eye, especially the retina-choroid complex, has an unusually high concentration of zinc compared to other tissues. The highest amount of zinc is concentrated in the retinal pigment epithelium (RPE) (RPE-choroid, 292± 98.5 µg gdry tissue), followed by the retina (12362.2 µg gdry tissue). The interplay between zinc and inflammation has been explored in other parts of the body but, so far, has not been extensively researched in the eye. Several lines of evidence suggest that ocular zinc concentration decreases with age, especially in the context of age-related disease. Thus, a hypothesis that retinal function could be modulated by zinc nutrition is proposed, and subsequently trialled clinically. In this review, the distribution and the potential role of zinc in the retina-choroid complex is outlined, especially in relation to inflammation and immunity, and the clinical studies to date are summarized.

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Insufficient zinc intake enhances lung inflammation in response to agricultural organic dust exposure.

PMID: 

J Nutr Biochem. 2019 Aug ;70:56-64. Epub 2019 May 3. PMID: 31153019

Abstract Title: 

Insufficient zinc intake enhances lung inflammation in response to agricultural organic dust exposure.

Abstract: 

Organic dust exposure particularly within hog confinement facilities is a significant cause of airway inflammation and lung disease. In a cohort of Midwestern veterans with COPD and agricultural work exposure we observed reduced zinc intakes which were associated with decreased lung function. Because insufficient zinc intake is common within the U.S. and a potent modulator of innate immune function, we sought to determine whether deficits in zinc intake would impact the airway inflammatory response to hog confinement facility dust extract (HDE). Adult male C57BL/6 mice were randomized to zinc deficient or matched zinc sufficient diets for 3 weeks and subsequently treated with intranasal HDE inhalation or saline once or daily for 3 weeks while maintained on specific diets. Lavage fluid and lung tissue was collected. Conditions of zinc deficiency were also studied in macrophages exposed to HDE. Single and repetitive HDE inhalation exposure resulted in increased influx of total cells and neutrophils, increased mediator hyper-responsiveness (TNFα, IL-6, CXCL1, and amphiregulin), and enhanced tissue pathology that was more pronounced in zinc deficient mice compared to normal dietary counterparts. Airway inflammation was most pronounced in zinc deficient mice treated with repetitive HDE for 3 weeks. Similarly, macrophages maintained in a zinc deficient environment exhibited increased CXCL1 and IL-23 production as a result of increased NF-κB activation. Conclusion: Given the relatively high incidence of dietary deficiencies in agriculture workers, we anticipate that zinc intake, or a lack thereof, may play an important role in modulating the host response to organic dust exposure.

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Role of zinc in immune system and anti-cancer defense mechanisms.

PMID: 

Nutrients. 2019 Sep 22 ;11(10). Epub 2019 Sep 22. PMID: 31546724

Abstract Title: 

Role of Zinc in Immune System and Anti-Cancer Defense Mechanisms.

Abstract: 

The human body cannot store zinc reserves, so a deficiency can arise relatively quickly, e.g., through an improper diet. Severe zinc deficiency is rare, but mild deficiencies are common around the world. Many epidemiological studies have shown a relationship between the zinc content in the diet and the risk of cancer. The anti-cancer effect of zinc is most often associated with its antioxidant properties. However, this is just one of many possibilities, including the influence of zinc on the immune system, transcription factors, cell differentiation and proliferation, DNA and RNA synthesis and repair, enzyme activation or inhibition, the regulation of cellular signaling, and the stabilization of the cell structure and membranes. This study presents selected issues regarding the current knowledge of anti-cancer mechanisms involving this element.

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