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Zinc Update: Zinc-dependent NF-κB signaling: Antioxidant and anti-inflammatory effects of zinc

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eMediNexus    01 December 2020

Zinc is a nutritionally fundamental trace element, essential to the structure and function of numerous macromolecules – including enzymes regulating cellular processes and cellular signaling pathways as per an article published in Inflammopharmacology. This mineral modulates immune response and exhibits antioxidant and anti-inflammatory activity.

The authors explained that zinc retards oxidative processes on a long-term basis by inducing the expression of metallothioneins. These metal-binding cysteine-rich proteins are responsible for maintaining zinc-related cell homeostasis and act as potent electrophilic scavengers and cytoprotective agents. Additionally, zinc increases the activation of antioxidant proteins and enzymes – such as, glutathione and catalase. Zinc exerts its antioxidant effect via two acute mechanisms, one of which is the stabilization of protein sulfhydryls against oxidation. The second mechanism consists in antagonizing transition metal-catalyzed reactions. Zinc can exchange redox active metals, such as copper and iron, in certain binding sites and attenuate cellular site-specific oxidative injury.

Researchers have found that physiological reconstitution of zinc restrains immune activation, whereas zinc deficiency, in the setting of severe infection, provokes a systemic increase in Nuclear Factor Kappa B (NF-κB) activation. Additionally, in vitro studies have shown that zinc decreases NF-κB activation and its target genes, such as TNF-α and IL-1β, and increases the gene expression of A20 and PPAR-α—the two zinc finger proteins with anti-inflammatory properties. Alternative NF-κB inhibitory mechanism is initiated by the inhibition of cyclic nucleotide phosphodiesterase, whereas another presumed mechanism consists in inhibition of IκB kinase in response to infection by zinc ions that have been imported into cells by ZIP8.

In inference, it was stated that zinc does not affect a single component of human immune system. It rather influences multiple aspects of the immune system – including hematopoiesis, innate immunity, adaptive immune response and processes involved in immune regulation. Since impaired zinc homeostasis, constantly increase proinflammatory cytokines and oxidative stress feature, prominently in multiple chronic diseases, zinc supplementation adjusted to the actual requirement may prove to be a useful preventive and therapeutic agent for human health.

Source: Inflammopharmacology. 2017; 25(1): 11–24.0020. Published online 2017 Jan 12. doi: 10.1007/s10787-017-0309-4

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