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Thiosemicarbazone derivate protects from AAPH and Cu2+ -induced LDL oxidation.

机译:硫代氨基脲类衍生物可防止AAPH和Cu2 +诱导的LDL氧化。

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AIMS: Several lines of evidence support the hypotheses that the oxidation of low density lipoprotein (LDL) may play a crucial role in the initiation and progression of atherosclerosis. Oxidative stress is one of the causes of the overproduction of reactive species that increase the formation of oxidized LDL. Thiosemicarbazones are compounds used in anticancer, antiviral and antifungal therapy; however, its redox activity has been controversial. Thus, we tested, in vitro, a possible antioxidant activity of a thiosemicarbazone derivate, the isatin-3-N(4)-benzilthiosemicarbazone (IBTC). MAIN METHODS: We measured the conjugated diene formation in serum and LDL as well as the loss of tryptophan fluorescence in LDL induced by two oxidant agents, 2,2-azobis(2-amidinopropane dihydrochloride) (AAPH) and Cu(2+). Thiobarbituric acid reactive substances (TBARS) formation in LDL and in different rat tissues was also assessed. The toxicity of IBTC was measured using aortic slices viability assay. KEY FINDINGS: Our results show that IBTC significantly reduced the AAPH and Cu(2+)-induced formation of conjugated dienes, increased in a dose-dependent manner the lag phase and the t(1/2) of tryptophan fluorescence, and reduced the TBARS formation in LDL, plasma and rat tissues, showing no toxicity to aortic slices. SIGNIFICANCE: These results indicate that IBTC is a good antioxidant and a promising antiatherogenic agent for further studies in vivo.
机译:目的:多种证据支持以下假设,即低密度脂蛋白(LDL)的氧化可能在动脉粥样硬化的发生和发展中起关键作用。氧化应激是反应物种过度产生的原因之一,反应物种增加了氧化LDL的形成。硫代氨基脲是用于抗癌,抗病毒和抗真菌治疗的化合物;但是,其氧化还原活性一直存在争议。因此,我们在体外测试了硫半脲类衍生物isatin-3-N(4)-苯并硫半脲(IBTC)的可能的抗氧化活性。主要方法:我们测量了血清和LDL中共轭二烯的形成,以及由两种氧化剂2,2-偶氮二(2-ami基丙烷二盐酸盐)(AAPH)和Cu(2+)诱导的LDL中色氨酸荧光的损失。还评估了低密度脂蛋白和不同大鼠组织中硫代巴比妥酸反应性物质(TBARS)的形成。 IBTC的毒性使用主动脉切片生存力测定法进行测量。关键发现:我们的结果表明,IBTC显着降低了AAPH和Cu(2+)诱导的共轭二烯的形成,以剂量依赖性方式增加了色氨酸荧光的滞后期和t(1/2),并降低了色氨酸的荧光强度。低密度脂蛋白,血浆和大鼠组织中的TBARS形成,对主动脉片无毒性。意义:这些结果表明,IBTC是一种良好的抗氧化剂,是有希望用于体内进一步研究的抗动脉粥样硬化剂。

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