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Although alpha-tocopheryl (vitamin E) is a potent antioxidant, many studies have demonstrated the radioprotective impact of alpha-tocopheryl acetate ester, emphasizing its antioxidant and anti-apoptotic effects; fewer studies were conducted using the succinate ester without any declaration of its anti-inflammatory effect in the concerned pathology. Accordingly, the current study was conducted to evaluate the dual antioxidant and anti-inflammatory role of alpha-tocopheryl succinate (\u03b1-TCS) in reproductive toxicity induced by gamma-irradiation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Animals were subjected to 6\u00a0Gy of whole-body gamma radiation and received \u03b1-TCS (200\u00a0mg\/kg, P.O.) pre- and post-radiation. After the termination of the experiment, serum testosterone was estimated, and the testis weight was recorded. Besides, the testicular content of oxidative balance markers [malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT)] and inflammatory response markers [interleukin-1\u03b2 (IL-1\u03b2), nuclear factor-kappa B (NF-\u03baB) p65, peroxisome proliferator-activated receptor-\u03b3 (PPAR-\u03b3)] were assessed.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Irradiated (IR) rats showed disturbances in the testicular function and abnormal incidental lesions, as demonstrated in the histopathological examinations. They exhibited marked alterations in the testicular oxidative  balance,  verified by the rise of lipid peroxidation\u00a0end product (MDA) and depletion of antioxidant enzymes (CAT and SOD). Also, radiation exposure triggered an inflammatory response, which was evidenced by suppression of PPAR-\u03b3  and intensified expression of NF-\u03baB p65 subunit, with subsequent elevation in IL-1\u03b2 testicular\u00a0content. Conversely, administering \u03b1-TCS to IR rats maintained the testicular architecture and ultrastructure while also preserving testicular function. Treatment with \u03b1-TCS restored the oxidative balance (MDA, SOD and CAT) and reduced testicular content of\u00a0pro-inflammatory cytokine IL-1\u03b2 via interference with the NF-\u03baB p65\/ PPAR-\u03b3 signaling pathway.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>The current study sheds light on the crucial radioprotective role of \u03b1-TCS as a PPAR-\u03b3 agonist in maintaining testicular function partially through suppressing NF-\u03baB activation and its downstream pro-inflammatory mediators.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s12906-025-04950-7","type":"journal-article","created":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T10:07:54Z","timestamp":1749463674000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Mitigation of radiation mediated testicular dysfunction by \u03b1-tocopheryl succinate: PPAR-\u03b3 related pathway"],"prefix":"10.1186","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5782-2908","authenticated-orcid":false,"given":"Heba A.","family":"Gheita","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2208-560X","authenticated-orcid":false,"given":"Ghada M.","family":"Shafey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1182-4443","authenticated-orcid":false,"given":"Maha M.","family":"Aziz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8856-2643","authenticated-orcid":false,"given":"Noha A.","family":"Fadel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,9]]},"reference":[{"key":"4950_CR1","doi-asserted-by":"publisher","first-page":"1492","DOI":"10.3390\/biomedicines12071492","volume":"12","author":"I Georgakopoulos","year":"2024","unstructured":"Georgakopoulos I, Kouloulias V, Ntoumas GN, Desse D, Koukourakis I, Kougioumtzopoulou A, Kanakis G, Zygogianni A. 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