Hasnaa Ali Ebrahim; Amal Alhakami; Saif A. Alqahtani; Youssef A. Alqahtani; Ayed A. Shati; Hailah M. Almohaimeed; Mohamed A. Haidara; Amal F. Dawood; Samah Elattar; Hala Koreatam & Helda Mechaeal
Diabetic nephropathy (DN) is a prevalent complication of diabetes, necessitating the development of effective therapies targeting the mechanisms by which type 2 diabetes mellitus (T2DM) induces renal tissue damage. In this study, DN was induced in rats using a high-fat diet for 13 weeks combined with streptozotocin to assess the effects of mesenchymal stem cells (MSCs) injection on renal tissues and function. Histological, immunohistochemistry, and biochemical analysis were employed to evaluate inflammation, oxidative stress, apoptosis, and histological architecture. The results demonstrated that MSCs improved metabolic derangement (glucose and lipid profile) and kidney function (urea and creatinine) associated with a significant reduction in inflammatory biomarkers: high sensitivity CRP (hs-CRP), tumour necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), as well as oxidative stress biomarkers :reactive: oxygen species (ROS) and superoxide dismutase (SOD). Additionally, MSCs administration upregulates peroxisome proliferator-activated receptor gamma (PPARγ) and nuclear factor erythroid 2-related factor 2 (Nrf2) expression levels. MSCs also show improved histological architecture associated with decreased CD45 (marker of inflammation) and caspase-3 (marker of apoptosis) immunostaining in renal tissues of the treated diabetic group. In conclusion, MSCs improved diabetic-induced nephropathy through suppression of oxidative stress, inflammation, apoptosis and upregulation of the Nrf2/PPAR-γ inflammatory signaling pathway.
KEY WORDS: Mesenchymal stem cells; Diabetic nephropathy; Oxidative stress; Nrf2/PPAR-γ signaling pathway.
EBRAHIM. H. A.; ALHAKAMI, A.; ALQAHTANI, S. A.; ALQAHTANI, Y. A.; SHATI, A. A.; ALMOHAIMEED, H. M.; HAIDARA, M. A.; DAWOOD, A. F.; ELATTAR, S.; KOREATAM, H. & MECHAEAL, H. Mesenchymal stem cells attenuate renal microscopic alterations in induced diabetic nephropathy in rats through suppression of oxidative stress, inflammation, apoptosis and upregulation of Nrf2/PPAR-γ inflammatory signaling pathway. Int. J. Morphol., 43(1):226-236, 2025.
