The effect of edoxaban on apoptosis in an abdominal aortic aneurysm model in rats.

Abstract

Background: This study aimed to evaluate the effects of edoxaban, which is used in venous thrombosis, systemic embolism, and stroke, on an aortic aneurysm model and to demonstrate the pharmacokinetic and molecular effects of edoxaban through the induction of apoptosis.

Methods: In this double-blind experimental study, 21 Wistar albino male rats (mean weight: 290 g; range, 280 to 300 g) were divided into three groups: the sham group (n=7), the abdominal aortic aneurysm (AAA) group (n=7), and the AAA-edoxaban group (n=7). Edoxaban 10 mg/kg was given to the AAA-edoxaban group by oral gavage daily for 30 days. At the end of 30 days, the aneurysmal aorta was surgically removed and histologically examined. The abdominal aorta was surgically exposed and wrapped with a calcium chloride (0.5 mol/L) sponge for 10 min.

Results: Immunohistochemically, aortic sections were marked with caspase-3 and caspase-9 antibodies. It was observed that the pathways that trigger apoptosis (caspase-3 and caspase-9; p <0.004 and p <0.005, respectively) were significantly reduced in the AAA-edoxaban group compared to the AAA group. In the AAA-edoxaban group, it was observed that the expansion in aortic diameter and the deterioration in the elastic fibril structure in the aortic aneurysm were decreased as a result of edoxaban treatment. Edoxaban treatment was observed to reduce cell death in both the tunica intima and tunica media.

Conclusion: This study provided strong evidence of the protective effect of edoxaban on aortic aneurysm-related vascular damage by reducing apoptosis and mitophagy.