Direct oral anticoagulant agents attenuate temporary aortic occlusion-induced renal oxidative and inflammatory responses in rats.

BACKGROUND

This study aims to investigate the effects of different direct oral anticoagulants on experimental renal injury induced by temporary infrarenal aortic occlusion.

METHODS

A total of 35 male Wistar rats (250 to 350 g) were randomly allocated to any of the five groups: sham, ischemia-reperfusion, rivaroxaban, dabigatran, and apixaban groups. Sham group underwent median laparotomy. Ischemia-reperfusion group was given saline gavage for one week. Animals in the other groups received rivaroxaban (3 mg/kg), dabigatran (15 mg/kg), or apixaban (10 mg/kg) daily once for one week via oral gavage. The infrarenal abdominal aorta was clamped for 60 min, and reperfusion was maintained for 120 min in the ischemia-reperfusion, rivaroxaban, dabigatran, and apixaban groups. At the end of reperfusion, kidneys were harvested for biochemical and histopathological analysis.

RESULTS

Renal total antioxidant capacity was reduced, and total oxidant status, interleukin-1 beta, and tumor necrosis factor-alpha were elevated in the ischemia-reperfusion group, compared to the sham group (p<0.005). Histological damage scores were also higher in the ischemia-reperfusion group (p<0.005). Administration of direct oral anticoagulants caused an increase of total antioxidant capacity and reduction of total oxidant status, tumor necrosis factor-alpha, and interleukin-1 beta in the rivaroxaban, dabigatran, and apixaban groups compared to the ischemia-reperfusion group (p<0.005). Histological damage scores were lower in the rivaroxaban and dabigatran groups than the ischemia-reperfusion group scores (p<0.005).

CONCLUSION

Direct oral anticoagulants reduce aortic clamping-induced renal tissue oxidation and inflammation. Rivaroxaban and dabigatran attenuate ischemia-reperfusion-related histological damage in kidneys.