# Zinc-Mediated Defenses Against Toxic Heavy Metals and Metalloids: Mechanisms, Immunomodulation, and Therapeutic Relevance

## TL;DR

Zinc helps protect against toxic heavy metals by supporting enzymes and immune function, and its supplementation is studied for health benefits.

## Contribution

This review highlights zinc's role in mitigating heavy metal toxicity and its therapeutic relevance in immune dysfunction and cancer.

## Key findings

- Zinc supplementation can counteract heavy metal toxicity by competing for binding sites and enhancing protective mechanisms.
- Dysregulation of zinc transporters (ZIPs/ZnTs) is linked to immune dysfunction and cancer progression.
- Recommended daily zinc intake varies by gender and health status, with higher doses suggested during deficiency.

## Abstract

Zinc (Zn), a naturally occurring trace element ubiquitous in the Earth’s crust, soil, and water, is indispensable for human health due to its physiological and nutritive benefits. In this scenario, Zn is pivotal for maintaining homeostasis against toxic effects exerted by heavy metals (HMs) through bioaccumulation and metabolic interference. Zinc is an enticing cofactor for miscellaneous biochemical enzymes such as Zn metalloenzymes, which mediate crucial cellular processes, including cell proliferation, protein synthesis, immune modulation, epigenetic regulation, and nucleic acid synthesis. Recently, several research studies have focused on the thorough investigation of Zn supplementation in controlling HM toxicity by competing for binding sites and boosting protective mechanisms in humans. The current article discusses the upper limits for various toxic HMs in staple crop foods, as provided by globally recognized organizations. Clinical studies recommend a daily dose of 11 mg of Zn for healthy men and 8–12 mg for women in healthy and pregnancy conditions. However, during Zn deficiency, therapeutic supplementation is expected to be adjustable, and the dosage is increased from 15 to 30 mg daily. This review discusses the dysregulation of specific Zn importers and transporters (ZIPs/ZnTs) due to their clinical significance in immune system dysfunction as well as the progression of a myriad of cancers, including prostate, breast, and pancreas. Moreover, this review emphasizes indispensable in vitro and in vivo studies, as well as key molecular mechanisms related to Zn supplementation for treating toxicities exacerbated by HMs.