{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T01:43:28Z","timestamp":1777081408571,"version":"3.51.4"},"reference-count":77,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T00:00:00Z","timestamp":1776988800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environmental Toxicology"],"abstract":"ABSTRACT<\/jats:title>\n \n Heavy metal mixtures (HMMs) containing lead (Pb), cadmium (Cd), and arsenic (As) induce oxidative stress and inflammation in thyroid and thymic tissues, disrupting endocrine and immune homeostasis. While\n \n Prosopis africana<\/jats:italic>\n <\/jats:styled-content>\n pod methanolic extract (PA) exhibits antioxidant properties, its protective mechanisms against multi\u2010metal toxicity remain undefined. This study investigated PA's efficacy in mitigating HMM\u2010induced organ injury in rats. Male Sprague\u2013Dawley rats (\n n<\/jats:italic>\n \u2009=\u20095\/group) received environmentally relevant HMM [PbCl\n 2<\/jats:sub>\n (20\u2009mg\/kg), CdCl\n 2<\/jats:sub>\n (1.61\u2009mg\/kg), Na\n 2<\/jats:sub>\n AsO\n 3<\/jats:sub>\n (10\u2009mg\/kg)] via drinking water with concurrent daily oral gavage of PA extract (500, 1000, or 1500\u2009mg\/kg) for 60\u2009days. Tissue metal accumulation was quantified by atomic absorption spectrophotometry and oxidative stress markers spectrophotometrically. Inflammatory mediators (TNF\u2010\u03b1), apoptotic markers (caspase\u20103), and pathway regulators (Nrf2, NF\u2010\u03baB) were measured by ELISA. Histopathological evaluation and multivariate analyses were performed. PA extract, rich in flavonoids and tannins, exhibited dose\u2010dependent protective effects. Co\u2010treatment significantly reduced Pb, Cd, and As accumulation in thyroid and thymus (up to 82% reduction in thyroid Cd at 1500\u2009mg\/kg compared to HMM controls,\n p<\/jats:italic>\n \u2009<\u20090.05). Oxidative balance was restored, evidenced by a 79% decrease in malondialdehyde and recovery of antioxidant enzyme activities (SOD, CAT, GSH, GPx). PA normalized dysregulated Nrf2 expression and suppressed NF\u2010\u03baB activation, restoring functional antioxidant responses, resulting in marked attenuation of TNF\u2010\u03b1 (95% reduction) and caspase\u20103 (76% reduction). These biochemical improvements correlated with the prevention of HMM\u2010induced organomegaly and preservation of normal histoarchitecture.\n \n Prosopis africana<\/jats:italic>\n <\/jats:styled-content>\n pod methanolic extract confers significant protection against HMM\u2010induced thyroid and thymic injury through dual mechanisms: (i) substantial reduction of tissue metal bioaccumulation (up to 82% reduction in thyroid Cd), and (ii) restoration of functional Nrf2\u2010mediated antioxidant responses while suppressing NF\u2010\u03baB\u2010driven inflammation. Critically, PA normalized suggesting dysregulated compensatory Nrf2 elevation while enhancing antioxidant enzyme activities, demonstrating functional pathway restoration rather than mere suppression. These findings highlight PA's potential as a multi\u2010targeted phytotherapeutic agent for mitigating heavy metal toxicity, warranting further mechanistic and translational studies.\n <\/jats:p>","DOI":"10.1002\/tox.70108","type":"journal-article","created":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T01:25:09Z","timestamp":1777080309000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prosopis africana<\/i>\n Pod Methanolic Extract Attenuates Multi\u2010Metal Oxidative Injury in Thyroid and Thymus: Evidence for Nrf2\/\n NF<\/scp>\n \u2010\n \u03baB<\/scp>\n Modulation and Implications for Environmental Toxicity"],"prefix":"10.1002","author":[{"given":"Harrison A.","family":"Ozoani","sequence":"first","affiliation":[{"name":"African Centre of Excellence for Public Health and Toxicological Research, University of Port Harcourt Port Harcourt Nigeria"},{"name":"Department of Pharmacology & Toxicology, Faculty of Pharmacy Enugu State, University of Science & Technology Enugu Nigeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7019-3555","authenticated-orcid":false,"given":"Kenneth O.","family":"Okolo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology & Toxicology, Faculty of Pharmacy Enugu State, University of Science & Technology Enugu Nigeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barido Donatus","family":"Dooka","sequence":"additional","affiliation":[{"name":"African Centre of Excellence for Public Health and Toxicological Research, University of Port Harcourt Port Harcourt Nigeria"},{"name":"Department of Experimental Pharmacology & Toxicology, Faculty of Pharmaceutical Sciences University of Port Harcourt Port Harcourt Nigeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cecilia N.","family":"Obasi","sequence":"additional","affiliation":[{"name":"Department of Experimental Pharmacology & Toxicology, Faculty of Pharmaceutical Sciences University of Port Harcourt Port Harcourt Nigeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8498-4021","authenticated-orcid":false,"given":"Prosper Manu","family":"Abdulai","sequence":"additional","affiliation":[{"name":"African Centre of Excellence for Public Health and Toxicological Research, University of Port Harcourt Port Harcourt Nigeria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5806-9858","authenticated-orcid":false,"given":"Orish E.","family":"Orisakwe","sequence":"additional","affiliation":[{"name":"Advanced Research Centre, European University of Lefke Lefke Northern Cyprus Cyprus"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,4,24]]},"reference":[{"key":"e_1_2_12_2_1","article-title":"Global Trends and Prospects in Research on Heavy 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