Protectıve Effects Of Dırect Oral Antıcoagulants In An Experimental Ischemıa-Reperfusıon Model

Abstract Objective The aim of this study was to investigate the protective effect of direct oral anticoagulants on skeletal muscle reperfusion injury in an experimental ischemia–reperfusion (IR) model. Methods 40 female Wistar albino rats were randomly divided into five groups: control, sham, apixaban, rivaroxaban and dabigatran. Sham group underwent only anesthesia and median laparotomy. Control group underwent the IR procedure. Apixaban group received 10 mg/kg twice daily, dabigatran group received 15 mg/kg once daily and rivaroxaban group received 3 mg/kg once daily by oral gavage for one week. IR procedure was performed as infrarenal aorta clamping for 60 min followed by 120 min of reperfusion. After the procedure, 2–3 cc intracardiac blood and bilateral gastrocnemius muscle samples were obtained from each group. Biochemical markers TAC,TOS,IL-1,IL-6 and TNF-α levels were analyzed in muscle tissue and blood. Histopathologically, inflammation, necrosis,congestion,fibrosis and atrophy levels in muscle tissue were examined. Results IL-6 levels were significantly lower in muscle and serum samples in the dabigatran group ( p < 0.001). In addition, TNF-a levels were significantly lower in the dabigatran group ( p = 0.003). Inflammation was also reduced in the rivaroxaban and apixaban groups, but not as markedly as in the dabigatran group. In histopathologic evaluations, muscle tissue damage was found to be the lowest in the dabigatran group. Antioxidant capacity (TAC) was higher in the dabigatran group ( p = 0.009), but there was no significant difference in TOS levels between the groups. Conclusion Direct oral anticoagulants showed anti-inflammatory and antioxidant effects against IR injury. In particular, dabigatran offered a more pronounced protective effect compared to other drugs with its effects on inflammation and oxidative stress.