Background: Atherosclerosis is a very common disease in which fat deposition in the inner layers of arteries leading to plaques formation.
Dapagliflozin is one of a new class of drugs known as the sodium?glucose cotransporter?2 inhibitors, responsible for lowering of the blood
glucose level, and enhancing urinary glucose excretion. Dapagliflozin may lower blood glucose levels and at the same time prevent cardiovascular
diseases. Objective: The objective of this study was to assess the effect of dapagliflozin on atherosclerosis through interfering with inflammatory
and oxidative pathways. Materials and Methods: Eighteen local domestic male rabbits were used in this study. The rabbits were randomly
divided into three groups: Group I rabbits fed normal chow diet for 12 weeks; Group II rabbits fed with 0.5% cholesterol?enriched diet; and
Group III rabbits fed with 0.5% cholesterol?enriched diet together with dapagliflozin (1 mg/kg once daily). Blood samples were collected
before the study (zero time) and every 4 weeks for the measurement of serum total cholesterol, triglycerides (TGs), high?density lipoprotein
cholesterol (HDL?C), low?density lipoprotein cholesterol (LDL?C), very LDL?C (VLDL?C), tumor necrosis factor alpha (TNF??), and
endothelin?1 (ET?1). Results: Dapagliflozin treatment showed insignificant elevation in total cholesterol and LDL?C, significant decrease
VLDL?C and TG, and significant elevation of HDL?C level (P < 0.05) compared with the induced untreated group. It was insignificantly
decreased inflammatory markers (TNF?? and ET?1), increased aortic total antioxidant capacity, and significantly reduced aortic intima thickness
compared with induced untreated group. Dapagliflozin, by slightly interfering with inflammatory and oxidative pathways, may show beneficial
effects on atherosclerosis and can attenuate the atherosclerotic lesion formation. Conclusion: Dapagliflozin may have a beneficial effect on
atherosclerosis by slightly interfering with inflammatory and oxidative pathways and can reduce the atherosclerotic lesion formation; however,
our study needs further clinical studies to be carried out on large population.