Evaluation of the effect of dapagliflozin on atherosclerosis progression by interfering with inflammatory and oxidative stress pathways in rabbits

Abstract EN

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‑α), 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‑α 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.