Impact of Dapagliflozin on Atherosclerosis through Inflammation and Oxidative Pathways

Abstract

Background: Atherosclerosis is a prevalent pathological disorder considered a leading cause of death globally. The pathological process is characterized by fat deposition in the blood vessels, ultimately developing plaques. The atherosclerotic plaque was the final result of the inflammatory reaction and oxidative pathway. Dabagliflozine is a member of hypoglycemic drugs that are classified based on their action as Na-glucose co-transporter 2 inhibitors. Dabagliflozine, besides its blood glucose-lowering effects, may also exhibit cardiovascular protection by reducing oxidative damage. Our research aimed to evaluate how the drug (dabagliflozine) interacted with inflammation and oxidative processes to impact atherosclerosis. Materials and Methods: In this study, eighteen male mice were split into three groups: one fed a regular diet, one fed a cholesterol-rich diet, and one fed a cholesterol-rich diet with dapagliflozin. Blood samples were taken regularly over twelve weeks to analyze serum markers such as TNF-α, endothelin-1, and lipid levels. Results: Initially, there were no significant differences in serum markers among the groups. However, after twelve weeks, the mice treated with dapagliflozin showed notable reductions in TNF-α and endothelin-1 levels (though statistically insignificant). Moreover, there were significant improvements in HDL (the "good" cholesterol) levels, and significant decreases in VLDL and TG (triglycerides) levels (P<0.05). Total cholesterol (TC) and LDL (the "bad" cholesterol) levels also decreased, although not significantly. Conclusion: In conclusion, dapagliflozin demonstrated promising protective effects against atherosclerosis in mice by regulating inflammatory cytokine production and improving lipid profiles. These findings suggest that dapagliflozin may have potential therapeutic benefits in managing cardiovascular disease by targeting both inflammation and lipid metabolism. However, further research is needed to validate these results and explore the drug's effectiveness in humans.