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Fish, being highly sensitive to environmental changes, serve as valuable models for monitoring the health of these ecosystems. Metallothionein (Mt), a biomarker for metal contamination, shows variable expression depending on the metal involved. Transcription of the\n                    <jats:italic>mt<\/jats:italic>\n                    gene is regulated by intracellular metal concentrations and mediated by interactions between metal\u2010responsive transcription factors (Mtf) and metal response elements (MRE) in the\n                    <jats:italic>mt<\/jats:italic>\n                    promoter. Zinc plays a key role by binding to Mtf, activating it, and enabling interaction with MRE sequences to initiate transcription. In this context, this study aimed to identify the most potent inducers of\n                    <jats:italic>mt<\/jats:italic>\n                    expression in\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Oreochromis niloticus<\/jats:italic>\n                    <\/jats:styled-content>\n                    . Initially, zinc\u2010binding proteins from\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>O. niloticus<\/jats:italic>\n                    <\/jats:styled-content>\n                    were modeled to assess differential binding scores of various metals using molecular docking, which suggested the potency ranking Cd\n                    <jats:sup>2+<\/jats:sup>\n                    \u2009&gt;\u2009Cu\n                    <jats:sup>2+<\/jats:sup>\n                    \u2009&gt;\u2009Mn\n                    <jats:sup>2+<\/jats:sup>\n                    \u2009&gt;\u2009Hg\n                    <jats:sup>2+<\/jats:sup>\n                    \u2009&gt;\u2009Pb\n                    <jats:sup>2+<\/jats:sup>\n                    . These predictions were validated using primary hepatocytes exposed to concentrations 10 times higher than the maximum allowed for effluent discharge under Brazilian law. The expression of both\n                    <jats:italic>mt<\/jats:italic>\n                    mRNA and Mt protein was evaluated in hepatocytes. Both\n                    <jats:italic>in silico<\/jats:italic>\n                    and in\u00a0vitro results identified cadmium as the most potent inducer of Mt. Other metals did not induce\n                    <jats:italic>mt<\/jats:italic>\n                    expression under the tested conditions. These findings underscore the importance of understanding how Mt expression varies by metal and tissue, as differences in responsiveness can influence the interpretation of Mt levels in teleost fish used for water quality monitoring and environmental toxicology.\n                  <\/jats:p>","DOI":"10.1002\/jat.4914","type":"journal-article","created":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T06:28:25Z","timestamp":1756880905000},"page":"590-600","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Multimodal Approach to Identify Metallothionein Metal Inducers in Nile Tilapia: Insights From Molecular Docking and Hepatocyte Exposure"],"prefix":"10.1002","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9379-4625","authenticated-orcid":false,"given":"Jessica\u00a0Zablocki","family":"da Luz","sequence":"first","affiliation":[{"name":"Grupo de Pesquisa em Toxicologia Celular, Departamento de 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