Dapagliflozin mitigates oxidative stress, inflammatory, and histopathological markers of aging in mice

Abstract

Aging, a complex physiological process affecting all living things, is a major area of research, particularly focused on interventions to slow its progression. This study assessed the antiaging efficacy of dapagliflozin (DAPA) on various aging-related parameters in a mouse model artificially induced to age. Forty male Swiss albino mice were randomly divided into four groups of ten animals each. The control group (Group I) received normal saline. The aging model group (Group II) was administered D-galactose orally at 500mg/kg to induce aging. Following the aging induction, the positive control group received Vitamin C supplementation (Group III), while the DAPA group (Group IV) was treated with dapagliflozin. The inflammatory mediators (TNF-α and IL-1β) showed similar patterns of change. No statistically significant difference was observed between groups III and IV. Both groups had significantly lower values compared to GII, while it was significantly higher compared to GI. Glutathione peroxidase (GSH-Px) showed no statistically significant difference between groups GIII and GIV, but it was higher in GIII compared to GII and significantly lower in GIII compared to GI. The study demonstrated that dapagliflozin exerts a beneficial impact on many indicators of aging in mice. The intervention resulted in a reduction in hypertrophy in cardiomyocytes, an enhancement in skin vitality, a decrease in the presence of inflammatory mediators, and an improvement in the efficacy of antioxidants.

Keywords: AGEs, Advanced Glycation End Products; CVD, Cardiovascular Disease; Ca2+, Calcium; Col-I, Collagen I; Col-III, Collagen III; DAPA, Dapagliflozin; Dapagliflozin; GSH-Px, Glutathione Peroxidase; H&E, Hematoxylin and Eosin Stain; HPF, High Power Fields; IL-1β, Interleukin-1 Beta; IP, Intraperitoneally; MDA, Malondialdehyde; ROS, Reactive Oxygen Species; SD, Standard Deviation; SGLT2, Sodium-Glucose Cotransporter-2; SGLT2i, Sodium-Glucose Cotransporter 2 Inhibitors; TNF-α, Tumor Necrosis Factor-Alpha; aging; heart; inflammation; oxidative stress; skin.

Figure 1

Study flowchart

Figure 2

Induction of the aging process in mice

Figure 3

Histological evaluation of cardiac tissue from Group I (H&E stain). Cardiac tissue section from Group I (treated with normal saline only) observed under light microscopy (Olympus BX51 microscope with DP controller software at 40x magnification). The image shows typical cardiac cell morphology with normal nuclei (indicated by black arrows).

Figure 4

Histological evaluation of cardiac tissue from Group II (H&E stain). Cardiac tissue section from Group II (treated with D-galactose only) observed under light microscopy (Olympus BX51 microscope with DP controller software at 40x magnification). The image highlights abnormal cardiac cells with irregular and hyperchromatic nuclei (indicated by black arrows).

Figure 5

Histological evaluation of cardiac tissue section from Group IV (H&E stain). Cardiac tissue section from Group IV (treated with 1 mg/kg DAPA) observed under light microscopy (Olympus BX51 microscope with DP controller software at 40x magnification). The section displays normal cardiac cells and nuclei, comparable to the control group.