PMID: 

Adv Nutr. 2019 Jul 1 ;10(4):696-710. PMID: 31305906

Abstract Title: 

The Role of Zinc in Antiviral Immunity.

Abstract: 

Zinc is an essential trace element that is crucial for growth, development, and the maintenance of immune function. Its influence reaches all organs and cell types, representing an integral component of approximately 10% of the human proteome, and encompassing hundreds of key enzymes and transcription factors. Zinc deficiency is strikingly common, affecting up to a quarter of the population in developing countries, but also affecting distinct populations in the developed world as a result of lifestyle, age, and disease-mediated factors. Consequently, zinc status is a critical factor that can influence antiviral immunity, particularly as zinc-deficient populations are often most at risk of acquiring viral infections such as HIV or hepatitis C virus. This review summarizes current basic science and clinical evidence examining zinc as a direct antiviral, as well as a stimulant of antiviral immunity. An abundance of evidence has accumulated over the past 50 y to demonstrate the antiviral activity of zinc against a variety of viruses, and via numerous mechanisms. The therapeutic use of zinc for viral infections such as herpes simplex virus and the common cold has stemmed from these findings; however, there remains much to be learned regarding the antiviral mechanisms and clinical benefit of zinc supplementation as a preventative and therapeutic treatment for viral infections.

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PMID: 

J Dermatol Sci. 2019 Aug ;95(2):62-69. Epub 2019 Jul 12. PMID: 31327530

Abstract Title: 

Zinc deficiency exacerbates pressure ulcers by increasing oxidative stress and ATP in the skin.

Abstract: 

BACKGROUND: Zinc deficiency is believed to be a predisposing factor for the development and intractable healing of pressure ulcers (PUs); however, the mechanisms of this association have not been elucidated.OBJECTIVE: Objective was to elucidate the mechanisms of the formation of severe and prolonged PUs under the zinc deficiency condition.METHODS: We assessed PUs formation after cutaneous ischemia-reperfusion (I/R) injury in mice fed with a zinc-adequate (ZA) or a zinc-deficient (ZD) diet from 2 weeks before I/R injury. Wound size, vascular damage, apoptotic cells, adenosine triphosphate (ATP) amount, and the number of Langerhans cells (LCs) in I/R area were analyzed. We evaluated the extent of oxidative stress in I/R area in OKD48 mice through bioluminescence detection.RESULTS: We found that dietary zinc deficiency caused the formation of severe and prolonged PUs in mice. Zinc deficiency increased the vascular disorder, oxidative stress, and apoptosis induced by cutaneous I/R injury. I/R injury-induced oxidative stress signals were significantly higher in ZD OKD48 mice than in ZA OKD48 mice. Additionally, zinc deficiency reduced the number of LCs and increased the amount of ATP in cutaneous I/R-injured skin. Oral supplementation of zinc improved zinc deficiency-associated PUs.CONCLUSION: Zinc deficiency might increase cutaneous I/R injury-induced vascular damages, oxidative stress, and apoptosis, as well as ATP amount in I/R area due to the loss of LCs. These mechanisms might partly account for zinc deficiency-induced formation of severe and prolonged PUs. Oral supplementation of zinc might be a reasonable therapeutic choice for patients with PUs and zinc deficiency.

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PMID: 

J Complement Integr Med. 2019 Aug 15. Epub 2019 Aug 15. PMID: 31421040

Abstract Title: 

Effects of zinc supplementation on oxidant/antioxidant and lipids status of pesticides sprayers.

Abstract: 

Background Excess exposure to pesticides induces oxidative stress and causes alteration in the lipid profile Objectives The study aimed to evaluate the effects of Zinc (Zn) supplementation on the oxidant/antioxidant and lipid status in pesticide sprayers. Methods Forty pesticide sprayers were included in the study. Blood lipids, malondialdehyde (MDA), glutathione peroxidase (GPx), superoxide dismutase (SOD), and Zn were estimated; before and after Zn supplementation. Results Statistical analysis revealed that after Zn supplementation, total cholesterol (TC), triglycerides (TG), low density lipoprotein (LDL), very low density lipoprotein (VLDL), and MDA were significantly decreased. However, there was a significant increase in the high density lipoprotein (HDL), SOD, GPx, and Zn levels. After Zn supplementation, significant inverse correlations were detected between the Zn and the levels of MDA, TG, and VLDL, while positive correlation between Zn and the levels of HDL and TC. Conclusions Zn supplementation improves the oxidative/antioxidants and lipid status in pesticide sprayers.

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PMID: 

J Matern Fetal Neonatal Med. 2019 Sep 12:1-6. Epub 2019 Sep 12. PMID: 31438733

Abstract Title: 

The influence of zinc supplementation on metabolic status in gestational diabetes: a meta-analysis of randomized controlled studies.

Abstract: 

Zinc supplementation has emerged as an important approach to improve metabolic status in gestational diabetes. However, its use has not been well established. We conduct a systematic review and meta-analysis to evaluate the efficacy of zinc supplementation to improve metabolic status for gestational diabetes.PubMed, Embase, and the Cochrane Central Register of Controlled Trials are searched. Randomized controlled trials (RCTs) assessing the influence of zinc supplementation (or its combination) versus placebo on metabolic status of gestational diabetes are included. Two investigators independently have searched articles, extracted data, and assessed the quality of included studies. Meta-analysis is performed using the random-effect model.Five RCTs involving 263 patients are included in the meta-analysis. Compared with control intervention for gestational diabetes, zinc supplementation is associated with significantly reduced FPG (std. MD = -0.52; 95% CI = -0.82 to -0.21; = .0008), insulin (std. MD = -0.68; 95% CI = -0.98 to -0.37; 

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PMID: 

Biol Trace Elem Res. 2019 Sep 7. Epub 2019 Sep 7. PMID: 31494808

Abstract Title: 

Effects of Zinc Supplementation on Cardiometabolic Risk Factors: a Systematic Review and Meta-analysis of Randomized Controlled Trials.

Abstract: 

The prevalence of cardiometabolic risk factors has been increasing worldwide. The results of reported studies on the effects of zinc supplementation on cardiometabolic risk factors are unequivocal. This systematic review and meta-analysis of randomized controlled trials was conducted to evaluate the effects of zinc supplementation on cardiometabolic risk factors. A systematic search was conducted through international databases (PubMed/Medline, Institute of Scientific Information, and Scopus) until December 2018 to include all randomized controlled trials (RCT), quasi-RCT, and controlled clinical trials which assessed the effect of zinc supplementation on cardiometabolic risk factors including lipid profile, glycemic indices, blood pressure, and anthropometric indices. Random- or fixed-effects meta-analysis method was used to estimate the standardized mean difference (SMD) and 95% confidence interval (CI). A total of 20 studies were included in the meta-analysis, which included a total of 1141 participants in the intervention group. Meta-analysis showed that zinc supplementation significantly decreased plasma levels of triglyceride (SMD – 0.66, 95% CI – 1.27, – 0.06), very-low-density lipoprotein (SMD – 1.59, 95% CI – 2.86, – 0.31), and total cholesterol (SMD – 0.65, 95% CI – 1.15, – 0.15). Similarly, zinc supplementation significantly decreased fasting blood glucose (SMD – 0.52, 95% CI – 0.96, – 0.07) and HbA1c (SMD – 0.64, 95% CI – 1.27, – 0.02). The effects of zinc supplementation on blood pressure and anthropometric indices were not statistically significant (P>0.05). Zinc supplements had beneficial effects on glycemic indices and lipid profile. Thus, it appeared that zinc supplementation might be associated with a decrease in cardiometabolic risk factors contributing to a reduction in risk of atherosclerosis.

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PMID: 

Behav Brain Res. 2019 Sep 20 ;377:112247. Epub 2019 Sep 20. PMID: 31545978

Abstract Title: 

Prenatal zinc supplementation attenuates lipopolysaccharide-induced behavioral impairments in maternal immune activation model.

Abstract: 

Maternal infection during pregnancy is considered a key risk factor for developing schizophrenia in offspring. There is evidence that maternal exposure to infectious agents is associated with fetal zinc deficiency. Due to the essential role of zinc in brain function and development, in the present study, we activated maternal immune system using lipopolysaccharide (LPS) as a model of schizophrenia to examine whether zinc supplementation throughout pregnancy can reverse LPS-induced deleterious effects. To test the hypothesis, pregnant rats were treated with intraperitoneal injection of either saline or LPS (0.5 mg/kg) at gestational day 15 and 16, and zinc supplementation (30 mg/kg) was administered throughout pregnancy by gavage. At postnatal day 60, Y-maze was used to evaluate working memory of offspring. Moreover, the expression levels of catechol O-methyltransferase (COMT) and glutamate decarboxylase 67 (GAD67) were measured in the frontal cortex of the brain samples. Only male offspring prenatally exposed to LPS showed a significant impairment in working memory. In addition, prenatal LPS exposure causes a moderate decrease in GAD67 expression level in the male pups, while COMT expression was found unchanged. Interestingly, zinc supplementation restored the alterations in working memory as well as GAD67 mRNA level in the male rats. No alteration was detected for neither working memory nor COMT/GAD67 genes expression in female offspring. This study demonstrates that zinc supplementationduring pregnancy can attenuate LPS-induced impairments in male pups. These results support the idea to consume zinc supplementation during pregnancy to limit neurodevelopmental deficits induced by infections in offspring.

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PMID: 

Front Neurosci. 2019 ;13:920. Epub 2019 Sep 4. PMID: 31551684

Abstract Title: 

Long-Term Effects of Zinc Deficiency and Zinc Supplementation on Developmental Seizure-Induced Brain Damage and the Underlying GPR39/ZnT-3 and MBP Expression in the Hippocampus.

Abstract: 

We previously illustrated that long-term upregulated expression of ZnT-3 in the hippocampus of rats that underwent neonatal seizures was restored by pretreatment with a ketogenic diet. It was recently demonstrated that upregulated expression of ZnT-3 was associated with increased concentrations of intracellular free zinc ions in anmodel of glutamate-induced hippocampal neuronal excitotoxic damage. However, there is still a lack of research on the effects of different concentrations of zinc in the diet on developmental convulsive brain injury. The aim of this study was to investigate the effects of different zinc concentrations in the diet on long-term neurobehavioral and seizure thresholds following lithium chloride-pilocarpine-induced developmental seizures. Sprague-Dawley rats (postnatal day 27, P27) were randomly assigned to one of six dietary groups for 4 weeks: normal zinc control group (Control group, 44 mg/kg Zn), Zn-deficient control group (ZD group, 2.7 mg/kg Zn), Zn supplemented control group (ZS group, 246 mg/kg Zn), pilocarpine-induced seizure plus regular zinc diet group (SE group, 44 mg/kg Zn), seizure plus low-zinc diet group (SE + ZD group, 2.7 mg/kg Zn), and seizure plus high-zinc diet group (SE + ZS group, 246 mg/kg Zn). Novel object recognition and passive avoidance tests were performed on rats at P42 and P56. After routine seizure threshold detection and Timm staining procedures at P57, expression of GPR39, ZnT-3, and MBP were detected in the hippocampus by Western blot analysis. The results revealed that the Zinc-deficient diet for 4 weeks aggravated the long-term adverse effects of developmental seizures, evidenced by weight, cognition, seizure threshold and serum zinc concentrations, which were paralleled by expression changes in hippocampal GPR39 and ZnT-3. In contrast, zinc supplementation for 4 weeks significantly improved damage-related changes described above and rescued the abnormal expression of GPR39, ZnT-3, and MBP in the hippocampus. Similar alterations between the expression pattern of MBP and aberrant sprouting of mossy fibers in the hippocampus may indicate that sprouting is a secondary pathological change caused by developmental brain damage rather than the cause of epileptogenesis. Up-regulation of MBP protein levels in the high zinc diet-treated seizure group as well as the corresponding improvement of cognitive impairment and reduced hippocampal mossy fiber regenerative sprouting, may represent a compensatory mechanism for neuronal membrane damage and repair.

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PMID: 

Paediatr Int Child Health. 2019 Oct 3:1-6. Epub 2019 Oct 3. PMID: 31578136

Abstract Title: 

Efficacy of zinc supplementation in the management of acute diarrhoea: a randomised controlled trial.

Abstract: 

: Zinc has been recommended for the treatment of acute diarrhoea; however, there are heterogeneous reports regarding its efficacy.: This study investigated the efficacy of zinc supplementation on the treatment outcomes of children admitted to hospital with acute diarrhoea.: A double-blind, randomised, placebo-controlled trial was conducted in the Srinakharinwirot University Hospital's Paediatric Department, Thailand. Eligible children were randomly allocated to receive either zinc bisglycinate (15 mg elemental zinc) or a placebo. The study protocol was registered in the Thai Clinical Trials Registry (TCTR20190423004).: Of 86 patients, 50 (58.1%) were male and the mean age (range) was 2.5 years (6 months to 9.3 years). The median (IQR) number of hours to recovery from diarrhoea was significantly less in the zinc group than in the controls [44 (24-48)52 (36-80) hours, respectively,0.01]. The median (IQR) number of stools was significantly lower in the zinc group [5 (3-12)] than in the controls [7 (4-17),= 0.02]. The median (IQR) duration of intravenous fluid therapy was 40 (24-56) hours in the zinc group and 56 (40-73) in the control group (< 0.01). The duration of hospitalisation was 60 (44-72) hours in the zinc group and 84 (56-136) hours in the controls (0.01). There was good compliance by all participants in both groups.: Zinc supplementation can reduce the time to resolution of acute diarrhoea, the length of hospital stay and the frequency of stools. Zinc supplementation is recommended as a routine strategy for Thai children with acute diarrhoea.

PMID: 

J Trace Elem Med Biol. 2019 Oct 11:126417. Epub 2019 Oct 11. PMID: 31653549

Abstract Title: 

Zinc supplements and bone health: The role of the RANKL-RANK axis as a therapeutic target.

Abstract: 

BACKGROUND: To this day, empirical data suggests that zinc has important roles in matrix synthesis, bone turnover, and mineralization and its beneficial effects on bone could be mediated through different mechanisms. The influence of zinc on bone turnover could be facilitated via regulating RANKL/RANK/OPG pathway in bone tissue. Therefore, the aim of the study was to conduct a review to investigate the possible effect of the zinc mediated bone remodeling via RANKL/RANK/OPG pathway.METHODS: A comprehensive systematic search was performed in MEDLINE/PubMed, Cochrane Library, SCOPUS, and Google Scholar to explore the studies investigating the effect of zinc as a bone remodeling factor via RANKL/RANK/OPG pathway regulation. Subsequently, the details of the pathway and the impact of zinc supplements on RANKL/RANK/OPG pathway regulation were discussed.RESULTS: The pathway could play an important role in bone remodeling and any imbalance between RANKL/RANK/OPG components could lead to extreme bone resorption. Although the outcomes of some studies are equivocal, it is evident that zinc possesses protective properties against bone loss by regulating the RANKL/RANK/OPG pathway. There are several experiments where zinc supplementation resulted in upregulation of OPG expression or decreases RANKL level. However, the results of some studies oppose this.CONCLUSION: It is likely that sufficient zinc intake will elicit positive effects on bone health by RANKL/RANK/OPG regulation. Although the outcomes of a few studies are equivocal, it seems that zinc can exert the protective properties against bone loss by suppressing osteoclastogenesis via downregulation of RANKL/RANK. Additionally, there are several experiments where zinc supplementation resulted in upregulation of OPG expression. However, the results of limited studies oppose this. Therefore, aside from the positive role zinc possesses in preserving bone mass, further effects of zinc in RANKL/RANK/OPG system requires further animal/human studies.

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PMID: 

Toxicol Mech Methods. 2019 Oct 1:1-9. Epub 2019 Oct 1. PMID: 31532279

Abstract Title: 

Zinc abrogates anticancer drug tamoxifen-induced hepatotoxicity by suppressing redox imbalance, NO/iNOS/NF-ĸB signaling, and caspase-3-dependent apoptosis in female rats.

Abstract: 

Tamoxifen (TAM) is used in breast cancer chemotherapy since its approval by the Food and Drug Administration in 1977. However, TAM therapy is accompanied with hepatotoxicity – a source of worry to clinicians. Oxidative stress and inflammation are the major implicated mechanisms contributing to TAM hepatotoxicity. In this study, we explored whether zinc (Zn) supplementation could prevent TAM-induced hepatotoxicity in female Wistar rats. Rats were subjected to oral pretreatment of Zn (100 mg/kg body weight (b.w.)/day) for 14 days against hepatic toxicity induced by single intraperitoneal administration of TAM (50 mg/kg b.w.) on day 13. TAM markedly elevated serum liver enzymes, whereas total protein and albumin considerably reduced. TAM caused prominent depletion of hepatic-reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activity. Also, TAM significantly increased malondialdehyde (MDA) level. Further, it raised liver levels of tumor necrosis factor-α (TNF-α), interleukin-1β, (IL-1β), interleukin-6 (IL-6), and nitricoxide (NO) confirmed by the liver histopathological alterations. The mechanistic inflammatory expression of inducible nitric oxide synthase (iNOS) and nuclear factor-kappa B (NF-ĸB), and expression of caspase-3 protein prominently increased. Zinc supplementation significantly modulated serum liverfunction markers, antioxidant enzymes, and GSH and MDA levels. Zinc downregulated the expression of cytokines, NO, iNOS, NF-ĸB and caspase-3, and ameliorated histopathological changes. Zinc protects against TAM-induced hepatotoxicity; it may serve as an adjuvant supplement for female patients undergoing TAM chemotherapy.

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