{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:46:34Z","timestamp":1786977994062,"version":"build-2736575974"},"reference-count":51,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T00:00:00Z","timestamp":1756857600000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"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":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Cadmium chloride (CdCl\u2082) is a powerful environmental toxin that has been documented to induce severe hepatic and renal damage through oxidative stress mechanisms. This study evaluated the protective impact of combined low dose of gamma irradiation (LDR) and trans\u2010resveratrol (Trans\u2010Res) on CdCl\u2082\u2010induced hepato\u2010renal toxicity in rats. Five groups of 50 male albino rats had been classified as; control, CdCl\u2082 (2\u2009mg\/kg), CdCl\u2082+LDR (0.75 Gray), CdCl\u2082+Trans\u2010Res (20\u2009mg\/kg\/b.wt.), and CdCl\u2082+Trans\u2010Res+LDR for 6 weeks. CdCl\u2082 significantly increased the enzymes of liver (alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [ALP]) and kidney markers (creatinine, urea), raised oxidative stress levels (hydrogen peroxide [H\u2082O\u2082], inducible nitric oxide synthase [iNOS]), lowered antioxidant activity superoxide dismutase (SOD), and increased fat breakdown products malondialdehyde (MDA) while causing inflammation (interleukin\u20106 [IL\u20106], nuclear factor kappa B [NF\u2010\u03baB]). Molecular analysis revealed that CdCl\u2082 downregulated Notch receptor 1 (Notch1) and Beta\u2010catenin (\u03b2\u2010catenin) genes with Wingless\u2010related integration site (Wnt) protein and upregulated Axis inhibition protein 2 (Axin2), Cellular myelocytomatosis oncogene (c\u2010myc), and Cyclin D genes with glycogen synthase kinase\u20103 beta (GSK\u20103\u03b2) and Hairy and enhancer of split 1 (HES1) proteins. Combined Trans\u2010Res+LDR treatment significantly reduced these biochemical alterations, controlled gene expression levels, and enhanced histopathological alterations in the kidney and liver tissues. In conclusion, our findings evidently indicate that trans\u2010resveratrol combined with low\u2010dose of gamma irradiation provides powerful protective effects against CdCl\u2082\u2010induced hepato\u2010renal injuries through redox homeostasis recovery, suppression of inflammatory mediators, and modulation of apoptotic signaling pathways, which suggest a new therapeutic approach against the toxicity of CdCl\u2082 heavy metal.<\/jats:p>","DOI":"10.1002\/jbt.70468","type":"journal-article","created":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T16:26:11Z","timestamp":1756916771000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["\u201cModulating Cadmium Chloride\u2010Induced Hepatorenal Damage: Interplay of Trans\u2010Resveratrol and Gamma Irradiation on Wnt\/\u03b2\u2010Catenin\/NOTCH and NF\u2010\u03baB Signaling Axes\u201d"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2609-9451","authenticated-orcid":false,"given":"Rokaya E.","family":"Maarouf","sequence":"first","affiliation":[{"name":"Radiation Biology Department, National Centre for Radiation Research and Technology (NCRRT) Egyptian Atomic Energy Authority Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7839-0112","authenticated-orcid":false,"given":"Hoda. A.","family":"Mansour","sequence":"additional","affiliation":[{"name":"Biological Applications Department, Nuclear Research Centre Egyptian Atomic Energy Authority Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatma Abdel\u2010Fattah M.","family":"Salem","sequence":"additional","affiliation":[{"name":"Chemistry Department Faculty of Science Helwan University Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4608-4540","authenticated-orcid":false,"given":"Marwa A.","family":"Esmat","sequence":"additional","affiliation":[{"name":"Radiation Biology Department, National Centre for Radiation Research and Technology (NCRRT) Egyptian Atomic Energy Authority Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,3]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph17113782"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines9121797"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jenvman.2020.110797"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2019.02.041"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envpol.2022.120879"},{"issue":"2","key":"e_1_2_12_7_1","first-page":"931","article-title":"Mitigating Cadmium Toxicity: Role of Caffeine in the Reduction of Oxidative Stress","volume":"15","author":"Aljazzar A.","year":"2025","journal-title":"Open Veterinary Journal"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.58332\/scirad2023v2i3a04"},{"issue":"1","key":"e_1_2_12_9_1","article-title":"Hormetic Responses in Normal Human Cell Lines After Low\u2010Dose Chronic Exposure to \u03b3\u2010Radiation","volume":"20","author":"Katsube T.","year":"2022","journal-title":"Dose\u2010Response"},{"key":"e_1_2_12_10_1","article-title":"\u201cMultiple Mechanisms of the Radiation\u2010Induced Bystander Effect Regulate Its Complex Biological Responses","volume":"13","author":"Fu H.","year":"2023","journal-title":"Frontiers in Oncology"},{"issue":"4","key":"e_1_2_12_11_1","first-page":"420","article-title":"Epigenetic Modifications in Response to Low\u2010Dose Radiation Exposure","volume":"96","author":"Zotova I. 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