Naser A ElSawy; Sameerah Shaheen; Ashraf Saleh; Naief A Dahran; Hawazen A AlGifry; Hany A. Elkattawy; Sahar K. Ali; Rania Naguib; Nada Mohamed Mohamed Soliman & Ahmed Algazeery

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by persistent hyperglycemia, leading to progressive damage to multiple organs. Among the serious complications, diabetic cardiomyopathy (DCM) is increasingly recognized as a major contributor to diabetes-related cardiovascular mortality. Sodium-glucose co-transporter-2 (SGLT2) inhibitors, such as empagliflozin (EMP), are well established as glucose-lowering agents; however, their direct protective mechanisms on cardiac tissue remain incompletely understood. This study aimed to explore the cardioprotective and molecular modulatory roles of EMP in a rat model of DCM. Forty male albino rats (180–200 g) were divided into four groups (n=10): control, vehicle, diabetic, and diabetic treated with EMP (10 mg/kg/day) for eight weeks. Cardiac tissues were analyzed histologically and immunohistochemically for aquaporin and a-smooth muscle actin (a- SMA) expression. Molecular changes were further assessed by quantifying Prkn gene expression, a key regulator of mitophagy. Empagliflozin treatment markedly improved cardiac histoarchitecture and reduced oxidative stress biomarkers compared to untreated diabetic rats. Immunohistochemical analysis revealed significant downregulation of aquaporin and a-SMA expression. Additionally, EMP treatment upregulated Prkn mRNA expression, indicating enhanced mitophagy activity within cardiomyocytes. Empagliflozin exerts a distinct cardioprotective effect in diabetic rats by modulating aquaporin channels, cytoskeletal remodeling, and Prkn-mediated mitophagy. These findings provide new mechanistic insights into the direct cardiac benefits of SGLT2 inhibition, supporting EMP as a promising therapeutic target for diabetic cardiomyopathy.

ELSAWY, N. A.; SHAHEEN, S.; SALEH, A.; DAHRAN, N. A.; ALGIFRY, H. A.; ELKATTAWY, H.A.; ALI, S. K.; NAGUIB, R.; SOLIMAN, N. M. M. & ALGAZEERY, A. Empagliflozin attenuates cardiac injury in STZ-induced diabetic rats by modulating aquaporins and a-smooth muscle actin. Int. J. Morphol., 44(4):1448-1460, 2026.