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Although it can be absorbed and accumulates in zebrafish muscle tissue, the potential effects on muscle tissue are still far from being studied. Thus, this study investigated the potential mechanism of TPhP\u2010induced muscle damage in zebrafish, focusing on oxidative stress and apoptosis. Elevated TPhP exposure concentration caused muscle tissue damage. TPhP could increase the activities of enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and glutathione S\u2010transferase (GST) involved in antioxidant effects in muscle tissue. Accordingly, oxidative stress caused by TPhP exposure also increased the levels of malondialdehyde (MDA), protein carbonyls, and 8\u2010hydroxy\u20102\u2032\u2010deoxyguanosine (8\u2010OHdG) in zebrafish muscle tissue, indicating that TPhP caused lipid peroxidation, protein oxidation, and DNA damage. In addition, TPhP exposure transcriptionally upregulated the nuclear factor E2\u2010related factor 2 (\n                    <jats:italic>nrf2<\/jats:italic>\n                    )\n                    <jats:italic>\u2013\u2013<\/jats:italic>\n                    Kelch\u2010like ECH\u2010associated protein 1 (\n                    <jats:italic>keap1<\/jats:italic>\n                    )\n                    <jats:italic>\u2013\u2013<\/jats:italic>\n                    antioxidant response element (ARE) (Nrf2\u2010Keap1\u2010ARE) signaling pathway, as evidenced by increased mRNA levels of downstream genes including\n                    <jats:italic>nrf2<\/jats:italic>\n                    , nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) quinone oxidoreductase 1 (\n                    <jats:italic>nqo1<\/jats:italic>\n                    ), heme oxygenase 1 (\n                    <jats:italic>ho1<\/jats:italic>\n                    ), glutamate\u2010cysteine ligase catalyst subunit (\n                    <jats:italic>gclc<\/jats:italic>\n                    ), and modifier subunit (\n                    <jats:italic>gclm<\/jats:italic>\n                    ). Concurrent transcriptional changes were also observed in apoptosis\u2010related genes such as tumor protein p53 (\n                    <jats:italic>tp53<\/jats:italic>\n                    ),\n                    <jats:italic>bcl2\u2010<\/jats:italic>\n                    associated X protein (\n                    <jats:italic>bax<\/jats:italic>\n                    ), B\u2010cell lymphoma 2 (\n                    <jats:italic>bcl2<\/jats:italic>\n                    ),\n                    <jats:italic>casp3<\/jats:italic>\n                    , and\n                    <jats:italic>casp9<\/jats:italic>\n                    , suggesting a potential link to apoptotic responses. Moreover, high\u2010concentration TPhP exposure increased uncoupling protein 2 (\n                    <jats:italic>ucp2<\/jats:italic>\n                    ) gene expression, revealing a regulatory role for\n                    <jats:italic>ucp2<\/jats:italic>\n                    in regulating oxidative stress. These findings not only provide histological and molecular evidence for the toxic effects of TPhP on zebrafish muscle tissue but also emphasize the urgency of conducting a comprehensive environmental risk assessment of TPhP to inform safety standards and risk management measures.\n                  <\/jats:p>","DOI":"10.1002\/jat.70258","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T12:27:14Z","timestamp":1780662434000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Triphenyl Phosphate Triggers Zebrafish Muscle Damage With Altered Expression of Genes Involved in Nrf2\u2010Keap1\u2010ARE Pathway\u2010Mediated Oxidative Stress and Apoptosis"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-9996-8462","authenticated-orcid":false,"given":"Yang","family":"Li","sequence":"first","affiliation":[{"name":"Department of Blood Transfusion Zhongnan Hospital of Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0201-9154","authenticated-orcid":false,"given":"Bin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Ultrasound, Zhongnan Hospital of Wuhan University Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9594-6217","authenticated-orcid":false,"given":"Yuqing","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Engineering China Pharmaceutical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4837-189X","authenticated-orcid":false,"given":"Lijuan","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Blood Transfusion Zhongnan Hospital of Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5587-6163","authenticated-orcid":false,"given":"Shuhan","family":"Li","sequence":"additional","affiliation":[{"name":"School of Engineering China Pharmaceutical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4359-3742","authenticated-orcid":false,"given":"Changxin","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Blood Transfusion Zhongnan Hospital of Wuhan University  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5579-5304","authenticated-orcid":false,"given":"Jianqiu","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Engineering China Pharmaceutical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5182-9685","authenticated-orcid":false,"given":"Likun","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine, Union Hospital, Tongji Medical College Huazhong University of Science and Technology  Wuhan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9916-8531","authenticated-orcid":false,"given":"Yanhua","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Engineering China Pharmaceutical University  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,5]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chemosphere.2019.124519"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.etap.2015.06.021"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/mas.21381"},{"issue":"11","key":"e_1_2_10_5_1","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.3390\/antiox12111953","article-title":"The Key Role of GSH in Keeping the Redox Balance in Mammalian Cells: Mechanisms and Significance of GSH in Detoxification via Formation of Conjugates","volume":"12","author":"Georgiou\u2010Siafis S. 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