P58 | VITAMIN D ATTENUATES LIVER INJURY BY REDUCING APOTOSIS, PYROPTOSIS, FERROPTOSIS AND PROMOTING REGENERATION IN TYPE 2 DIABETES

S. Rzeyeva¹, N. Bayromava², T. Ozbilenler¹, A. Akdemir³, M. Anapalı Aykaç⁴, D. Aydemir⁵, F. Kaya Dagistanli¹, T. Ulutin¹, O. Uysal¹, M. Ozturk⁶ | ¹Istanbul University-Cerrahpasa, Faculty of Medicine, Istanbul, Türkiye; ²Istanbul University-Cerrahpasa, Faculty of Medicine, Istanbul, Türkiye; ³Karabuk University, Faculty of Medicine, Karabük, Türkiye; ⁴Ataturk University, Faculty of Medicine, Erzurum, Türkiye; ⁵Istanbul University, Faculty of Medicine, Istanbul, Türkiye; ⁶Istanbul University-Cerrahpasa, Faculty of Medicine, Istanbul Türkiye

High-fructose diets are strongly implicated in the pathogenesis of type 2 diabetes mellitus (T2DM) and associated liver injury¹. Vitamin D (VitD) deficiency has been linked to increased insulin resistance and progression of liver fibrosis². This study aimed to evaluate the regenerative and protective effects of VitD in a modified T2DM rat model³. Sprague-Dawley rats were divided into four groups: Diabetic, VitD-treated Diabetic (170 IU/week orally from week 5), VitD-only, and Control. T2DM was induced using 10% fructose in drinking water and a single STZ dose (40 mg/kg). Metabolic parameters (glucose, weight, calorie intake) were recorded. Liver tissues were analyzed histologically (hematoxylin-eosin, Van Gieson, PAS, Prussian blue) for fibrosis, glycogen and iron deposition, and bile duct regeneration. Morphometric analysis quantified bile ducts in periportal regions. Oxidative stress (GSH/ GSSG), inflammation, and cell death pathways (pyroptosis, ferroptosis, apoptosis) were examined using immunohistochemistry for NLRP3, GSDMD, GPX4, TGFβ1, Caspase-3, αSMA, VDR, Ki67, YAP/TAZ, SIRT1, OV6, and TUNEL assays. Diabetic rats showed persistent hyperglycemia, hepatocellular vacuolization, iron overload, fibrosis, and elevated TGFβ1, αSMA, NLRP3, GSDMD, and apoptotic markers, with decreased GPX4 and GSH/GSSG ratio, indicating ferroptosis. VitD treatment ameliorated hyperglycemia, hepatic fibrosis, oxidative stress, inflammation, and regulated cell death in diabetics. It restored antioxidant status and increased Ki67, VDR, YAP/TAZ, SIRT1, and OV6 expression, indicating enhanced regeneration and progenitor activation. These findings support the therapeutic potential of VitD in managing fructoseinduced diabetic liver injury by modulating oxidative stress, inflammation, and cell death, while promoting hepatic repair.