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The balance between metal deficiency and excess is typically ensured by several extracellular and intracellular mechanisms involved in uptake, distribution, and excretion. However, provoked by either intrinsic or extrinsic factors, excess iron, zinc, copper, or manganese can lead to cellular damage upon chronic or acute exposure, frequently attributed to oxidative stress. Intracellularly, mitochondria are the organelles that require the tightest control concerning reactive oxygen species production, which inevitably leaves them to be one of the most vulnerable targets of metal toxicity. Current therapies to counteract metal overload are focused on chelators, which often cause secondary effects decreasing patients\u2019 quality of life. New therapeutic options based on synthetic or natural antioxidants have proven positive effects against metal intoxication. In this review, we briefly address the cellular metabolism of transition metals, consequences of their overload, and current therapies, followed by their potential role in inducing oxidative stress and remedies thereof.<\/jats:p>","DOI":"10.3390\/ijms25147880","type":"journal-article","created":{"date-parts":[[2024,7,18]],"date-time":"2024-07-18T14:59:50Z","timestamp":1721314790000},"page":"7880","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Metabolic Derangement of Essential Transition Metals and Potential Antioxidant Therapies"],"prefix":"10.3390","volume":"25","author":[{"given":"Adriana","family":"Fontes","sequence":"first","affiliation":[{"name":"Institute of Molecular Toxicology and Pharmacology, Helmholtz Center Munich, German Research Center for Environmental Health, D-85764 Neuherberg, Germany"},{"name":"CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"CIBB-Center for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-504 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8578-0919","authenticated-orcid":false,"given":"Adrian T.","family":"Jauch","sequence":"additional","affiliation":[{"name":"School of Medicine and Health, Institute of Toxicology and Environmental Hygiene, Technical University Munich, D-80802 Munich, Germany"}]},{"given":"Judith","family":"Sailer","sequence":"additional","affiliation":[{"name":"School of Medicine and Health, Institute of Toxicology and Environmental Hygiene, Technical University Munich, D-80802 Munich, Germany"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4233-0868","authenticated-orcid":false,"given":"Jonas","family":"Engler","sequence":"additional","affiliation":[{"name":"School of Medicine and Health, Institute of Toxicology and Environmental Hygiene, Technical University Munich, D-80802 Munich, Germany"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3295-1284","authenticated-orcid":false,"given":"Anabela Marisa","family":"Azul","sequence":"additional","affiliation":[{"name":"CNC-Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"CIBB-Center for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"IIIUC-Institute for Interdisciplinary Research, University of Coimbra, 3030-789 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4047-1566","authenticated-orcid":false,"given":"Hans","family":"Zischka","sequence":"additional","affiliation":[{"name":"Institute of Molecular Toxicology and Pharmacology, Helmholtz Center Munich, German Research Center for Environmental Health, D-85764 Neuherberg, Germany"},{"name":"School of Medicine and Health, Institute of Toxicology and Environmental Hygiene, Technical University Munich, D-80802 Munich, Germany"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Jomova, K., Makova, M., Alomar, S.Y., Alwasel, S.H., Nepovimova, E., Kuca, K., Rhodes, C.J., and Valko, M. 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