{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T21:48:29Z","timestamp":1789422509400,"version":"build-2803163510"},"reference-count":42,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T00:00:00Z","timestamp":1757376000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T00:00:00Z","timestamp":1757376000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81560513"],"award-info":[{"award-number":["81560513"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Humans' exposure to arsenic (As) has been associated with the development of various diseases. Some health effects may be mediated by arsenic\u2010induced toxicity to the thyroid and endocrine systems, but its underlying mechanisms remain unclear. The overall aim of our study was focused on using sodium arsenite (NaAsO\n                    <jats:sub>2<\/jats:sub>\n                    )\u2010exposed rats to investigate the involvement of the phosphatidylinositol 3\u2010kinase (PI3K) and transcription factor NF\u2010E2\u2010related factor 2 (Nrf2) pathways in toxicity to the thyroid and endocrine systems. In our in\u00a0vitro study, exposure of thyroid cells (a thyroid follicular epithelial cell line) to 0, 0.4, 0.8, and 3.2\u2009\u03bcM. NaAsO\n                    <jats:sub>2<\/jats:sub>\n                    caused reduced triiodothyronine (T3) and thyroxine (T4) levels, significantly increased estrogen receptor alpha (ER\u03b1) and thyroid hormone receptor alpha (TR\u03b1) mRNA levels, reduced Kelch\u2010like epichlorohydrin\u2010associated protein\u20101 (Keap1) and AKT serine (AKT) mRNA expression, and increased Nrf2 and PI3K mRNA expression (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). In the in\u00a0vivo study, Wistar rats were treated with 0, 0.8, 4.0, and 20.0\u2009mg\/kg\/d of NaAsO\n                    <jats:sub>2<\/jats:sub>\n                    for 20\u2009weeks. The exposure caused dose\u2010dependent histopathological changes in the thyroid, a significant increase in serum estradiol (E2), accompanied by alterations in thyroid hormone metabolism, as evidenced by decreased triiodothyronine (TG), T3, and T4 (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). Additionally, mRNA expression levels of ER\u03b1 and TR\u03b1 were significantly altered in the thyroid tissues. Keap1, Nrf2, PI3K, and AKT mRNA expression levels were increased (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05). Specifically, exposure to NaAsO\n                    <jats:sub>2<\/jats:sub>\n                    disrupted normal thyroid functions by regulating the PI3K\/Nrf2 pathway. Our findings indicate that NaAsO\n                    <jats:sub>2<\/jats:sub>\n                    exposure induced cytotoxicity and disrupted estrogen production both in\u00a0vivo and in\u00a0vitro investigations, leading to thyroid dysfunction through altered expression of the PI3K\/Nrf2 pathway. These findings highlight the complex mechanisms through which arsenic disrupted thyroid function and endocrine homeostasis.\n                  <\/jats:p>","DOI":"10.1002\/jat.4905","type":"journal-article","created":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T06:29:46Z","timestamp":1757485786000},"page":"833-844","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Involvement of the PI3K\/Nrf2 Pathway in Arsenic\u2010Induced Endocrine and Thyroid Toxicity in Rats"],"prefix":"10.1002","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-3886-3353","authenticated-orcid":false,"given":"Xiaowei","family":"Ma","sequence":"first","affiliation":[{"name":"School of Public Health, Key Laboratory of Special Environmental and Health Research Xinjiang Medical University  Urumqi 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