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This study aimed to evaluate whether pentahydroxy flavone (PHF) and Metformin (MET) could mitigate liver damage associated with streptozotocin (STZ)\u2010induced diabetes in rats exposed to gamma irradiation (IR). Diabetes was induced in rats by a single dose of STZ (35\u00a0mg\/kg) and exposure to a cumulative IR dose (4\u00a0Gy). Over one month, each treatment group received either PHF (50\u00a0mg\/kg) or MET (200\u00a0mg\/kg). Combined treatment with PHF and MET improved lipid profiles, reduced insulin resistance, coupled with diminishing hepatic inflammation (NLRC4) and oxidative stress. Furthermore, co\u2010administration of PHF and MET modulated the AMPK\/ SREBP1c\/ SCD1\u2010related signaling, ameliorating hepatic steatosis and fibrosis. These findings suggest that PHF combined with MET's could serve as an adjuvant therapy alongside MET to protect against liver damage caused by diabetes and gamma radiation.<\/jats:p>","DOI":"10.1002\/cbdv.71801","type":"journal-article","created":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T06:56:58Z","timestamp":1792565818000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pentahydroxyflavone and Metformin Mitigate Diabetes\u2010Induced Hepatic Dysfunction in Gamma\u2010Irradiated Rats Through the AMPK\u2010SREBP\u20101c\u2010SCD1 Pathway"],"prefix":"10.1002","volume":"23","author":[{"given":"Hanaa F.B.","family":"Gaber","sequence":"first","affiliation":[{"name":"Biochemistry and Molecular Biology Department Faculty of Veterinary Medicine Benha University  Al\u2010Qalyubia Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5792-0815","authenticated-orcid":false,"given":"Fatma S.M.","family":"Moawed","sequence":"additional","affiliation":[{"name":"Health Radiation Research National Center for Radiation Research and Technology Egyptian Atomic Energy Authority  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed K.","family":"Mahfouz","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Biology Department Faculty of Veterinary Medicine Benha University  Al\u2010Qalyubia Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5358-4394","authenticated-orcid":false,"given":"Esraa S.A.","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Radiation Biology Research National Center for Radiation Research and Technology Egyptian Atomic Energy Authority  Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1752-6709","authenticated-orcid":false,"given":"Omayma A.R.","family":"Abo\u2010Zaid","sequence":"additional","affiliation":[{"name":"Biochemistry and Molecular Biology Department Faculty of Veterinary Medicine Benha University  Al\u2010Qalyubia Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,20]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.21608\/bvmj.2024.327643.1881"},{"issue":"9","key":"e_1_2_11_3_1","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.4239\/wjd.v12.i9.1479","article-title":"Non\u2010Alcoholic Fatty Liver Disease in Diabetes: When to Refer to the Hepatologist?","volume":"12","author":"Khandelwal R.","year":"2021","journal-title":"World Journal of Diabetes"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.21608\/bvmj.2023.213632.1664"},{"issue":"2","key":"e_1_2_11_5_1","doi-asserted-by":"crossref","first-page":"S127","DOI":"10.2337\/dcS13-2011","article-title":"Pathophysiologic Approach to Therapy in Patients With Newly Diagnosed Type 2 Diabetes","volume":"36","author":"DeFronzo R. 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