Pentahydroxyflavone and Metformin Mitigate Diabetes‐Induced Hepatic Dysfunction in Gamma‐Irradiated Rats Through the AMPK‐SREBP‐1c‐SCD1 Pathway

ABSTRACT

Diabetes mellitus (DM) is a common complication among cancer patients, potentially worsening the adverse effects of radiation therapy. This study aimed to evaluate whether pentahydroxy flavone (PHF) and Metformin (MET) could mitigate liver damage associated with streptozotocin (STZ)‐induced diabetes in rats exposed to gamma irradiation (IR). Diabetes was induced in rats by a single dose of STZ (35 mg/kg) and exposure to a cumulative IR dose (4 Gy). Over one month, each treatment group received either PHF (50 mg/kg) or MET (200 mg/kg). Combined treatment with PHF and MET improved lipid profiles, reduced insulin resistance, coupled with diminishing hepatic inflammation (NLRC4) and oxidative stress. Furthermore, co‐administration of PHF and MET modulated the AMPK/ SREBP1c/ SCD1‐related 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.