Modulation of Inflammatory Markers by Vitamin D and Pioglitazone to Combat Renal Dysfunction in Type 2 Diabetic Rats

Abstract

Aim: This study is designed to assess the outcomes of Vitamin D (Vit D) and Pioglitazone (PIO) on metabolic
control, kidney function, inflammatory markers, and histopathology in rats with streptozotocin-nicotinamideinduced
diabetes. Materials and Methods: Rats were randomly assigned to five groups: Normal control, diabetic
control (DC), Vit D-treated, PIO-treated, and combined Vit D + PIO-treated, with treatments administered
orally for 8 weeks. Blood samples were analyzed for glucose, insulin, homeostasis model assessment of insulin
resistance (HOMA-IR), blood urea nitrogen (BUN), creatinine, and inflammatory markers, and kidney tissues were
assessed histopathologically after euthanasia. Results: Both Vit D and PIO treatments reduced glucose, insulin,
and HOMA-IR levels, with the combined treatment showing the most significant improvements, suggesting a
synergistic effect. Both Vit D and PIO also reduced serum creatinine and BUN levels, with the combination
therapy leading to a more substantial reduction in creatinine, although no significant improvement in BUN was
observed compared to Vit D alone. The combination therapy significantly reduced C-reactive protein, monocyte
chemoattractant protein-1, and interleukin-6 levels compared to the DC, though no additional benefits were
observed for tumor necrosis factor-alpha, cystatin-C, and transforming growth factor-beta 1. Histopathological
analysis revealed mild degenerative changes in the DC group, while the combined Vit D + PIO treatment
restored kidney structure to near normal, with minimal vascular congestion. Conclusion: Overall, both Vit D
and PIO positively impacted glucose regulation, kidney function, and inflammatory markers in diabetic rats, with
combination therapy showing superior efficacy, particularly in improving metabolic control and kidney histology.