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A comparison of multifunctional donors of carbon monoxide: Their anticoagulant, antioxidant, anti-aggregatory and cytotoxicity activities in an in vitro model.
Nitric Oxide ( IF 3.9 ) Pub Date : 2020-01-30 , DOI: 10.1016/j.niox.2020.01.010
Weronika Adach 1 , Beata Olas 1
Affiliation  

The study examines the effect of two water-soluble carbon monoxide (CO) donors, CORM-3 and CORM-A1, on selected parameters of oxidative stress and hemostasis in human plasma and blood platelets in vitro. It also compares their activity with that of the lipid-soluble CORM-2. The oxidation of amino acid residues in plasma proteins was evaluated by measuring the amounts of thiol and carbonyl groups. Plasma lipid peroxidation was measured as thiobarbituric acid reactive substance (TBARS) concentration. In addition, three haemostatic parameters of plasma were studied, viz. activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time (TT), and one haemostatic parameter of platelets (platelet aggregation). Treatment with CORM-3 and CORM-A1 (all concentrations from 0.1 to 100 μM) decreased thiol group oxidation induced by H2O2/Fe. Incubation with CORM-3 and CORM-A1 also influenced plasma coagulation activity, e.g. CORM-3 and CORM-A1 significantly prolonged TT at the two highest tested concentrations (50 and 100 μM). Only CORM-2 at the highest tested concentration (100 μM) and CORM-3 (50 and 100 μM) reduced platelet aggregation induced by ADP. None of the tested CORMs caused platelet damage. The treatment of various diseases associated with oxidative stress, including cardiovascular diseases, may be enhanced by the administration of CO donors CORM-2 and CORM-3, these being modulators of oxidative stress and hemostasis.

中文翻译:

一氧化碳多功能供体的比较:体外模型中的抗凝剂,抗氧化剂,抗聚集剂和细胞毒性活性。

这项研究检查了两种水溶性一氧化碳(CO)供体CORM-3和CORM-A1对体外人血浆和血小板氧化应激和止血所选参数的影响。它还将它们的活性与脂溶性CORM-2的活性进行了比较。通过测量硫醇和羰基的量来评估血浆蛋白中氨基酸残基的氧化。血浆脂质过氧化作为硫代巴比妥酸反应性物质(TBARS)的浓度进行测量。另外,还研究了血浆的三个止血参数。激活部分凝血活酶时间(APTT),凝血酶原时间(PT)和凝血酶时间(TT),以及血小板的一个止血参数(血小板聚集)。用CORM-3和CORM-A1(所有浓度从0.1到100μM)处理可减少H2O2 / Fe诱导的硫醇基氧化。与CORM-3和CORM-A1一起孵育也会影响血浆凝结活性,例如,在两个最高测试浓度(50和100μM)下,CORM-3和CORM-A1显着延长了TT。只有最高测试浓度(100μM)和CORM-3(50和100μM)的CORM-2才能减少ADP诱导的血小板凝集。所测试的CORM均未引起血小板损伤。可以通过给予CO供体CORM-2和CORM-3来增强与氧化应激相关的各种疾病(包括心血管疾病)的治疗,这些都是氧化应激和止血的调节剂。只有最高测试浓度(100μM)和CORM-3(50和100μM)的CORM-2才能减少ADP诱导的血小板凝集。所测试的CORM均未引起血小板损伤。可以通过给予CO供体CORM-2和CORM-3来增强与氧化应激相关的各种疾病(包括心血管疾病)的治疗,这些都是氧化应激和止血的调节剂。只有最高测试浓度(100μM)和CORM-3(50和100μM)的CORM-2才能减少ADP诱导的血小板凝集。所测试的CORM均未引起血小板损伤。可以通过给予CO供体CORM-2和CORM-3来增强与氧化应激相关的各种疾病(包括心血管疾病)的治疗,这些都是氧化应激和止血的调节剂。
更新日期:2020-01-31
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