The Effect of Zinc Sulfate Treatment on Diabetic Cardiomyopathy in an Aged Female Rat Model of Type 2 Diabetes.

Background/

Objectives

Diabetic cardiomyopathy (DCM) is largely driven by severe oxidative stress and calcium dyshomeostasis. We examined the targeted antioxidant and therapeutic effects of zinc sulfate (ZnSO4) on contractile dynamics, oxidative damage, calcium turnover, and apoptosis/fibrosis in aged female rats with type 2 diabetes.

Methods

Thirty-two aged female Wistar rats were divided into Control, Control + ZnSO4, Diabetes (DM), and DM + ZnSO4 groups. DM was induced via high-fat diet and 30 mg/kg streptozotocin. After a 4-week complication period, treatment groups received 10 mg/kg/day ZnSO4 (i.p.) for 6 weeks. Left ventricular papillary muscle contraction, oxidative/antioxidant markers (MDA/GSH), and gene expressions (SIRT1, GLUT4, SERCA2a, RyR2, Cav1.2, PLN) were evaluated. Myocardial architecture, fibrosis, and apoptosis were analyzed immunohistochemically. In DM rats, contractile force (CF) and velocities (±dF/dtmax) significantly declined.

Results

Concurrently, SIRT1, GLUT4, SERCA2a, RyR2, Cav1.2, and antioxidant GSH decreased, while oxidative lipid damage (MDA), PLN, Caspase-3 activity, Collagen I, and fibrosis increased (p < 0.001). ZnSO4 treatment in diabetic rats acted as a potent antioxidant modulator; it restored redox balance, activated the SIRT1/GLUT4 pathway, protected calcium-handling proteins from oxidative degradation, and significantly improved contractile dynamics. It also preserved myocardial architecture by reducing apoptosis and fibrosis. In healthy rats, ZnSO4 caused mild stress and early fibrosis.

Conclusions

In conclusion, while inducing mild stress in healthy myocardium, zinc supplementation provides robust antioxidant protection in diabetic hearts. It activates SIRT1, suppresses oxidative damage, maintains calcium homeostasis, and restores contractile dynamics, demonstrating strong antioxidant therapeutic potential against DCM.