Both red blood cell distribution width and mean platelet volume are found to be associated with the severity of atherosclerotic disease in patients with peripheral arterial disease. This finding hypothesizes that complete blood counting parameters may serve as a beneficial and cost-effective method for monitoring atherosclerotic peripheral disease.
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 6 h, and plasma levels of nitrogen oxide (NOx), prolidase and malondialdehyde (MDA) were obtained after 30 min of reperfusion. The sham group did not receive any drugs. Oral rivaroxaban (3 mg/kg) was administrated to Group III, intraperitoneal enoxaparin sodium (250 U/kg) was administrated to Group IV, and intraperitoneal bemiparine sodium (250 U/kg) was administrated to Group V 1 week prior to the induction of peripheral ischemia (for 6 h)-reperfusion. After 30 min 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 ± 17.3 μmol/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 ± 10.8 μmol/L, respectively) when compared with the sham group (Group II) (75.6 ± 24.3 μmol/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 ± 574.7 U/g in V (bemiparine sodium) than in the control group (144.6 ± 131.8 U/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).
The aim of this study was to investigate whether anticoagulant and antiaggregant agents have protective effects against oxidative damage induced by peripheral ischemia-reperfusion (I/R). Groups were created as follows: control group, I/R group (sham group), I/R plus acetylsalicylic acid (Group I), I/R+clopidogrel (Group II), I/R+rivaroxaban (Group III), I/R+bemiparin sodium (Group IV), and I/R+enoxaparin sodium (Group V). In Groups I, II, III, IV, and V, drugs were administered daily for 1 week before I/R creation. Peripheral I/R was induced in the I/R groups by clamping the right femoral artery. The rats were sacrificed 1 hour after reperfusion. Nitrogen oxide levels, malondialdehyde (MDA) levels, paraoxonase-1 (PON1) activity, and prolidase activity were evaluated in both cardiac and renal tissues. There was no significant difference in nitrogen oxide levels between the groups. However, cardiac and renal MDA were significantly higher and PON1 activity was markedly lower in the I/R groups compared with the control group (p<0.05). Although elevated prolidase activity was detected in both the cardiac and renal tissue of the I/R groups, only the sham group and Group V had significantly higher renal prolidase activity (p<0.05). Group V had significantly higher cardiac MDA, PON1, prolidase levels, and renal prolidase activity compared with the sham group (p<0.05). Significant improvement in renal MDA levels was only observed in Group III, and marked improvement was observed in the cardiac MDA levels of Group II when compared with the sham group (p<0.05). Thromboprophylactic agents appear to provide partial or prominent protection against I/R injury.
Antithrombotic agents play important roles in the prophylactic and therapeutic management of many cardiovascular disorders. Therefore, many researchers have focused on developing new strategies for anticoagulation. New oral anticoagulants and factor Xa inhibitors are products of such research. Although they are identified as advantageous, there are limited data available about their multisystemic interactions. Thus, the antiangiogenic behaviors of oral factor Xa inhibitors and low molecular weight heparins (LMWHs) were investigated in this study. The chick chorioallantoic membrane (CAM) model was designed to investigate the antiangiogenic potential of new oral factor Xa inhibitors (rivaroxaban) and LMWHs (enoxaparin sodium and tinzaparin sodium). Four different molar concentrations (10, 10, 10, and 10 μmol/l) were studied for each drug. Each concentration was studied on 20 fertilized eggs. Vessel structures were evaluated under a stereoscopic microscope, and vessel formation was scaled according to previous literature. Both enoxaparin and tinzaparin sodium have increased antiangiogenic efficacy on CAM in a dose-dependent manner. However, this increased efficacy did not reach significant levels (average score < 0.5). On the contrary, while rivaroxaban showed dose-dependent antiangiogenic properties similar to enoxaparin and tinzaparin, a significant average antiangiogenic score (0.7) was detected at 10 μmol/l concentrations. New oral anticoagulants seem to be more favorable. However, their safety for the cardiovascular system needs to be clarified through microsystem studies on, for example, angiogenesis.
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