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Therefore, the present study evaluated the combined exposure of lead acetate (Pb) and zinc oxide\u2010nanoparticles (ZnO\u2010NPs) compared to each metal alone on the thyroid gland of adult rats. A total of 30 adult male albino rats were divided into four groups, group I (control), group II received Pb (10\u00a0mg\/kg), group III received ZnO\u2010NPs (85\u2009mg\/kg) and group IV co\u2010administrated the two metals in the same previous doses. The materials were gavaged for 8\u2009weeks. The toxicity was assessed through several biochemical parameters. Our results revealed significant body weight reduction relative to increased thyroid weights, decreased both of serum\u2010free triiodothyronine (FT3), tetra\u2010iodothyronine (FT4), increased thyroid\u2010stimulating hormone (TSH), increased serum and thyroid levels of Pb and zinc, significant elevation in tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1), reduction in interleukin 4 (IL4), upregulation of Bax, and downregulation of Bcl\u20102 genes. Additionally, there was significant overexpression of nuclear factor erythroid 2\u2010related factor 2(Nrf2), 8\u2010Hydroxydeoxyguanosine(8\u2010OHdG), the elevation of tissues malondialdehyde (MDA), reduction of tissues total antioxidant capacity (TAC), and disruptive thyroid structural alterations in all metals groups with marked changes in the combined metals group. In conclusion, the combined exposure of Pb and ZnO\u2010NPs induced pronounced toxic thyroid injury, pointing to additive effects in rats than the individual metal effects through different significant changes of disruptive thyroid structural alterations related to the loading of thyroid tissues with Pb and zinc metals producing oxidative stress that mediated inflammation and apoptosis.<\/jats:p>","DOI":"10.1002\/tox.23373","type":"journal-article","created":{"date-parts":[[2021,9,23]],"date-time":"2021-09-23T14:56:58Z","timestamp":1632409018000},"page":"2589-2604","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Combined lead and zinc<scp>oxide\u2010nanoparticles<\/scp>induced thyroid toxicity through<scp>8\u2010OHdG<\/scp>oxidative stress\u2010mediated inflammation, apoptosis, and Nrf2 activation in rats"],"prefix":"10.1002","volume":"36","author":[{"given":"Eman El\u2010Sayed","family":"Khayal","sequence":"first","affiliation":[{"name":"Forensic Medicine and Clinical Toxicology Department, Faculty of Medicine Zagazig University Zagazig Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanaa M.","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Pathology Department, Faculty of Medicine Zagazig University Zagazig Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5233-1990","authenticated-orcid":false,"given":"Amany Mohamed","family":"Shalaby","sequence":"additional","affiliation":[{"name":"Histology and Cell Biology Department, Faculty of Medicine Tanta University Tanta Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed Ali","family":"Alabiad","sequence":"additional","affiliation":[{"name":"Pathology Department, Faculty of Medicine Zagazig University Zagazig Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arwa A.","family":"El\u2010Sheikh","sequence":"additional","affiliation":[{"name":"Forensic Medicine and Clinical Toxicology Department, Faculty of Medicine Zagazig University Zagazig Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,9,23]]},"reference":[{"key":"e_1_2_10_2_1","unstructured":"OECD (Organization for Economic Co\u2010operation and Development) Considerations for Assessing the Risks of Combined Exposure to Multiple Chemicals Series on Testing and Assessment No 296 Environment Health and Safety Division Environment Directorate (2018).https:\/\/www.oecd.org\/chemicalsafety\/risk\u2010assessment\/considerations\u2010for\u2010assessing\u2010the\u2010risks\u2010of\u2010combined\u2010exposure\u2010to\u2010multiple\u2010chemicals.pdf. 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