Factor-Xa inhibitors protect against systemic oxidant damage induced by peripheral-ischemia reperfusion

Abstract

Factor-Xa inhibitors are often used for prophylaxis and for the treatment of thrombotic vascular disorders. However, it is not known whether they are beneficial during the recanalization of the thrombotic vascular segment and during tissue reperfusion. Herein, we describe an animal study that was designed to investigate the possible protective effects and antioxidant properties of factor-Xa inhibitors. Forty rats were included in the study and were randomly divided into five equal groups. The first group served as a control group from which we obtained basal oxidant and antioxidant parameters. Peripheral ischemia was induced in the second group (sham group) for 6h, and plasma levels of nitrogen oxide (NOx), prolidase and malondialdehyde (MDA) were obtained after 30min of reperfusion. The sham group did not receive any drugs. Oral rivaroxaban (3mg/kg) was administrated to Group III, intraperitoneal enoxaparin sodium (250U/kg) was administrated to Group IV, and intraperitoneal bemiparine sodium (250U/kg) was administrated to Group V 1week prior to the induction of peripheral ischemia (for 6h)-reperfusion. After 30min of reperfusion, blood samples were obtained and NOx, prolidase and MDA levels in these groups were detected, and the rats were sacrificed. NOx levels were statistically similar (p>0.05) between Groups I, II, III, IV, and V (20.7±10.4, 17.4±9.7, 25.9±24.2, 27.0±11.9, 23.3±17.3μmol/L, respectively). MDA levels were significantly lower (p<0.05) in Groups III (rivaroxaban), IV (enoxaparin sodium), and V (bemiparine sodium) (24.9±11.9, 25.9±4.4, 25.4±10.8μmol/L, respectively) when compared with the sham group (Group II) (75.6±24.3μmol/L). Prolidase levels were higher (p>0.05) in the ischemia reperfusion groups (659.2±130.6 in II (sham), 1,741.0±1,530.6 in III (rivaroxaban), 2,453.8±1,590.4 in IV (enoxaparin sodium), and 889.2±574.7U/g in V (bemiparine sodium) than in the control group (144.6±131.8U/g). Ischemia-reperfusion events may occur in prothrombotic disorders. During these events, prophylactic or therapeutic factor-Xa inhibitors can protect against thrombosis and oxidative reperfusion injury. The new oral factor-Xa inhibitor, rivaroxaban, appears to provide the same antioxidant support as injectable low molecular weight heparins (LMWHs).