{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T11:58:05Z","timestamp":1790251085711,"version":"4.1.0"},"reference-count":169,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T00:00:00Z","timestamp":1759881600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Basic Science Research Program through the National Research Foundation of Korea (NRF)","award":["RS-2021-NR060117"],"award-info":[{"award-number":["RS-2021-NR060117"]}]},{"name":"Basic Science Research Program through the National Research Foundation of Korea (NRF)","award":["E429020401"],"award-info":[{"award-number":["E429020401"]}]},{"name":"Northwest Institute of Eco Environment and Resources, Chinese Academy of Sciences","award":["RS-2021-NR060117"],"award-info":[{"award-number":["RS-2021-NR060117"]}]},{"name":"Northwest Institute of Eco Environment and Resources, Chinese Academy of Sciences","award":["E429020401"],"award-info":[{"award-number":["E429020401"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Zinc (Zn), a naturally occurring trace element ubiquitous in the Earth\u2019s 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\u201312 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.<\/jats:p>","DOI":"10.3390\/ijms26199797","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T14:06:53Z","timestamp":1759932413000},"page":"9797","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Zinc-Mediated Defenses Against Toxic Heavy Metals and Metalloids: Mechanisms, Immunomodulation, and Therapeutic Relevance"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4800-9982","authenticated-orcid":false,"given":"Roopkumar","family":"Sangubotla","sequence":"first","affiliation":[{"name":"Department of Chemical, Biological, and Battery Engineering, Gachon University, 1342, Seongnam Daero, Seongnam-si 13120, Gyeonggi-Do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3394-7335","authenticated-orcid":false,"given":"Shameer","family":"Syed","sequence":"additional","affiliation":[{"name":"Key Laboratory of Ecological Safety and Sustainable Development in Arid Lands, Northwest Institute of Eco-Environment and Resources, Chinese Academy of Sciences, Lanzhou 730000, China"},{"name":"Drylands Salinization Research Station, Northwest Institute of Eco-Environment and Resources, Chinese Academy of Sciences, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6333-6175","authenticated-orcid":false,"given":"Anthati","family":"Mastan","sequence":"additional","affiliation":[{"name":"Department of Microbiology, School of of Sciences, Jain (Deemed to be University), Bengaluru 560027, Karnataka, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Buddolla Anantha","family":"Lakshmi","sequence":"additional","affiliation":[{"name":"Department of Electronic Engineering, Gachon University, 1342 Seongnam-Daero, Seongnam-si 13120, Gyeonggi-Do, Republic of Korea"},{"name":"Department of Semiconductor Engineering, Gachon University, 1342 Seongnam-Daero, Seongnam-si 13120, Gyeonggi-Do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jongsung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, and Battery Engineering, Gachon University, 1342, Seongnam Daero, Seongnam-si 13120, Gyeonggi-Do, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e04691","DOI":"10.1016\/j.heliyon.2020.e04691","article-title":"Heavy metal pollution in the environment and their toxicological effects on humans","volume":"6","author":"Briffa","year":"2020","journal-title":"Heliyon"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Knopf, B., and Konig, H. 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