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

Abstract

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 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.