Mechanism Of Zinc Action Research Articles

The Mechanisms of Zinc Action as a Potent Anti-Viral Agent: The Clinical Therapeutic Implication in COVID-19.

The pandemic of COVID-19 was caused by a novel coronavirus termed as SARS-CoV2 and is still ongoing with high morbidity and mortality rates in the whole world. The pathogenesis of COVID-19 is highly linked with over-active immune and inflammatory responses, leading to activated cytokine storm, which contribute to ARDS with worsen outcome. Currently, there is no effective therapeutic drug for the treatment of COVID-19. Zinc is known to act as an immune modulator, which plays an important role in immune defense system. Recently, zinc has been widely considered as an anti-inflammatory and anti-oxidant agent. Accumulating numbers of studies have revealed that zinc plays an important role in antiviral immunity in several viral infections. Several early clinical trials clearly indicate that zinc treatment remarkably decreased the severity of the upper respiratory infection of rhinovirus in humans. Currently, zinc has been used for the therapeutic intervention of COVID-19 in many different clinical trials. Several clinical studies reveal that zinc treatment using a combination of HCQ and zinc pronouncedly reduced symptom score and the rates of hospital admission and mortality in COVID-19 patients. These data support that zinc might act as an anti-viral agent in the addition to its anti-inflammatory and anti-oxidant properties for the adjuvant therapeutic intervention of COVID-19.

Zinc supplementation prevents the development of thymic involution induced by tumor growth in mice

Aim. The aim of this study was to investigate the influence of zinc supplementation on the development of thymic involution during the growth of transplantable tumor in mice. Materials and methods. Inbred C3HA mice after subcutaneous syngeneic hepatoma 22a inoculation received zinc sulfate with drinking water. After 3 weeks of tumor growth animals were killed, and evaluated for zinc content in serum blood samples, thymus status and parameters of tumor growth. Results. At the 21 day of tumor 22a growth weight and cellular content of the thymus were decreased by 3 times and endogenous zinc content in samples of blood serum was decreased by 1,9 times. Oral zinc sulfate supplementation at concentration of 22 mkg/ml in drinking water during 3 weeks, started from the first day after tumor inoculation, increased thymus weight and cellularity as well as serum zinc content. At the same time, it did not influence tumor size and survival rate of mice with hepatoma 22a. As a possible mechanism of zinc action, we studied the influence of zinc supplementation on the activity of two anti-oxidative defense enzymes: Cu,Zn-superoxide dismutase and catalase in the thymus. Zinc supplementation had no influence on these parameters, both remained at a higher level in tumor-bearing mice. Conclusion. Oral zinc supplementation in hepatoma 22a bearing mice induced retards the development of thymic involution with no influence on the tumor growth per se. The study allows to suggest that oral zinc administration may be considered as a prospective strategy for thymus reconstitution in oncology patients.

Zinc treatment ameliorates diarrhea and intestinal inflammation in undernourished rats.

BackgroundWHO guidelines recommend zinc supplementation as a key adjunct therapy for childhood diarrhea in developing countries, however zinc’s anti-diarrheal effects remain only partially understood. Recently, it has been recognized that low-grade inflammation may influence stunting. In this study, we examined whether oral zinc supplementation could improve weight, intestinal inflammation, and diarrhea in undernourished weanling rats.MethodsRats were undernourished using a northeastern Brazil regional diet (RBD) for two weeks, followed by oral gavage with a saturated lactose solution (30 g/kg) in the last 7 days to induce osmotic diarrhea. Animals were checked for diarrhea daily after lactose intake. Blood was drawn in order to measure serum zinc levels by atomic absorption spectroscopy. Rats were euthanized to harvest jejunal tissue for histology and cytokine profiles by ELISA. In a subset of animals, spleen samples were harvested under aseptic conditions to quantify bacterial translocation.ResultsOral zinc supplementation increased serum zinc levels following lactose-induced osmotic diarrhea. In undernourished rats, zinc improved weight gain following osmotic diarrhea and significantly reduced diarrheal scores by the third day of lactose intake (p < 0.05), with improved jejunum histology (p < 0.0001). Zinc supplementation diminished bacterial translocation only in lactose-challenged undernourished rats (p = 0.03) compared with the untreated challenged controls and reduced intestinal IL-1β and TNF-α cytokines to control levels.ConclusionAltogether our findings provide novel mechanisms of zinc action in the setting of diarrhea and undernutrition and support the use of zinc to prevent the vicious cycle of malnutrition and diarrhea.

Zinc: The New Antidepressant?

Low serum zinc levels have been linked to major depression. Furthermore, zinc treatment has been shown to have an antidepressant effect. With the hope of understanding the role of zinc in mood disorders, recent work has begun to explore possible mechanisms of zinc action on serotonin uptake in the brain.

Zinc: The New Antidepressant?

Low serum zinc levels have been linked to major depression. Furthermore, zinc treatment has been shown to have an antidepressant effect. With the hope of understanding the role of zinc in mood disorders, recent work has begun to explore possible mechanisms of zinc action on serotonin uptake in the brain.

Zinc and immunity: Molecular mechanisms of zinc action on T helper cells

AbstractThe essentiality of zinc for humans was recognized in 1963. It is now evident that nutritional deficiency of zinc in human populations throughout the developing world is common. The major factor responsible for this deficiency is the consumption of mainly cereal proteins rich in phytate. The clinical manifestations of zinc deficiency include growth retardation and male hypogonadism in the adolescents, rough skin, poor appetite, mental lethargy, delayed wound healing, cell‐mediated immune dysfunctions, and abnormal neurosensory disorders. A conditioned deficiency of zinc has been observed in many diseased states. In this work I have summarized our current knowledge concerning the molecular mechanisms of zinc action on T helper cells. Our studies showed that in zinc‐deficient HUT‐78 cells, phosphorylated IκB and Iκk, ubiquitinated IκB, and binding of nuclear factor (NF)‐κB to DNA were significantly decreased. Zinc increased the translocation of NF‐κB from cytosol to nucleus. These data show that zinc plays an important role in the activation of NF‐κB in HUT‐78 cells. We showed a significant effect of zinc on gene expression of interleukin (IL)‐2 and IL‐2 receptors α and β. We also showed that a decrease in gene expression of IL‐2 and its receptors in zinc‐deficient HUT‐78 cells may be the result of decreased activation of NF‐κB in zinc‐deficient cells. J. Trace Elem. Exp. Med. 16:139–163, 2003. © 2003 Wiley‐Liss, Inc.

Inhibitory effect of zinc-chelating dipeptide on parathyroid hormone-stimulated osteoclast-like cell formation in mouse marrow cultures: involvement of calcium signaling.

A possible mechanism of zinc action inhibiting the PTH-induced osteoclast-like cell formation in mouse marrow culture system in vitro was investigated. Bone marrow cells were cultured for 7 days in alpha-minimal essential medium containing a well-known bone-resorbing agent parathyroid hormone (1-34) (PTH). Osteoclast-like cell formation was estimated with staining for tartrate-resistant acid phosphatase (TRACP), a marker enzyme of osteoclasts. The effect of zinc sulfate (10(-6) M) or beta-alanyl-L-histidinato zinc (AHZ; 10(-6) M) inhibiting the PTH (10(-8) M)-induced osteoclast-like cell formation was clearly seen in the absence or presence of theophylline (10(-4) M). However, zinc compounds did not inhibit the stimulatory effect of dibutyryladenosine 3',5'-cyclic monophosphate (DBcAMP; 10(-4) M) on osteoclast-like cell formation. The stimulating effect of PTH (10(-8) M) on osteoclast-like cell formation was clearly weakened (about 50%) in the presence of EGTA (1.0 mM) or dibucaine (10(-5) M). Phorbol 12-myristate 13-acetate (PMA), a protein kinase C activator (10(-8) to 10(-6) M), clearly stimulated osteoclast-like cell formation. PMA effect was inhibited by the presence of AHZ (10(-6) M) or zinc sulfate (10(-8) M). However, the inhibitory effect of zinc compounds was not seen in the presence of both PTH (10(-8) M) and PMA (10(-6) M). The present findings suggest that zinc compounds inhibit PTH-stimulated osteoclast-like cell formation mediated through the Ca(2+)-dependent activation of protein kinase C.

The role of zinc as a stimulating factor in bone formation.

The role of zinc as a stimulatory factor on bone formation was reviewed. Bone growth retardation is a common finding in various conditions associated with zinc deficiency. The mechanism of zinc action on bone metabolism, however, has not been clarified so far. The oral administration of zinc sulfate (0.5-10 mg Zn/100 g body weight) to weanling rats can produce an increase in dry weight, alkaline phosphatase activity, calcium, collagen and deoxyribonucleic acid (DNA) contents in the femoral diaphysis, indicating that zinc has a stimulatory effect on bone formation and calcification. In tissue culture by using the calvaria from weanling rats, it has been demonstrated that zinc (10-6-10-4M) can stimulate bone protein synthesis, and that the zinc effect is based on activation of aminoacyl-transfer ribonucleic acid (tRNA) synthetase. The depletion of endogenous zinc in bone cells by treatment with dipicolinate, a chelator of zinc, can retard the synthesis of bone protein. Zinc is an essential factor in the systhesis of bone protein. Increasing age induces the deterioration of bone metabolism, and it decreases bone cellular zinc and protein systhesis. These decreases, however, can be restored by supplement of zinc. Thus, it has been introduced that zinc, an essential trace element, plays an important role in the stimulation of bone formation.