Dose-Dependent Protective Effect of Vitamin D on High-Fat Diet–Induced Liver Injury in Adult Male Rats: Anatomical and Immunohistology Study

Ali Abdull Sattar Abdull Jabar

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Ali Abdull Sattar Abdull Jabar
[email protected]
College of Medicine, University of Sumer, Al-Rifai, Iraq

Vol. 3 No. 10 (2025): International Journal of Integrative and Modern Medicine

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October 6, 2025

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Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disorder worldwide. While vitamin D deficiency correlates with NAFLD severity, comprehensive preclinical evidence linking vitamin D supplementation to multi-level hepatoprotection—including molecular mechanisms—is limited. This study aimed to evaluate the dose-dependent protective effects of vitamin D against high-fat diet (HFD)-induced NAFLD in rats, integrating anatomical, biochemical, histopathological, oxidative, inflammatory, and gene expression analyses. Forty male Wistar rats were randomized into four groups (n=10): Control, HFD, HFD + Vit D 500 IU/kg/day, and HFD + Vit D 2000 IU/kg/day for 12 weeks. Assessments included liver weight, serum ALT/AST, hepatic triglycerides, oxidative stress markers (MDA, SOD, GSH), serum cytokines (TNF-α, IL-6), histopathology (H&E, Oil Red O, Masson’s trichrome), fibrosis quantification (Sirius Red, α-SMA IHC), and hepatic mRNA expression of key genes (SREBP-1c, FAS, PPAR-α, CPT-1, TNF-α, TGF-β1, α-SMA, Collagen I). HFD induced severe steatosis, inflammation, oxidative stress, and early fibrosis, with elevated serum transaminases, hepatic TG, MDA, TNF-α, and IL-6, alongside downregulation of PPAR-α/CPT-1 and upregulation of lipogenic/fibrogenic genes. Vitamin D supplementation, especially at 2000 IU/kg, dose-dependently reversed all these alterations: normalizing liver architecture, reducing NAS from 6.6 to 1.4, suppressing collagen deposition by >75%, restoring redox balance, and modulating gene expression toward a hepatoprotective profile (p < 0.001 vs. HFD for most endpoints). Vitamin D exerts robust, dose-dependent protection against HFD-induced NAFLD through coordinated antioxidant, anti-inflammatory, anti-steatotic, and anti-fibrotic actions, validated at anatomical, biochemical, histological, and molecular levels. These findings provide a mechanistic foundation for vitamin D as a potential adjunctive therapy in human NAFLD.

Jabar, A. A. S. A. (2025). Dose-Dependent Protective Effect of Vitamin D on High-Fat Diet–Induced Liver Injury in Adult Male Rats: Anatomical and Immunohistology Study. International Journal of Integrative and Modern Medicine, 3(10), 1–17. Retrieved from https://medicaljournals.eu/index.php/IJIMM/article/view/2157

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International Journal of Integrative and Modern Medicine

Dose-Dependent Protective Effect of Vitamin D on High-Fat Diet–Induced Liver Injury in Adult Male Rats: Anatomical and Immunohistology Study

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