Kładna Aleksandra, Marchlewicz Mariola, Piechowska Teresa, Kruk Irena, Aboul-Enein Hassan Y
Department of History of Medicine and Medical Ethics, Pomeranian Medical University, Szczecin, Poland.
Department of Aesthetic Dermatology, Pomeranian Medical University, Szczecin, Poland.
Luminescence. 2015 Nov;30(7):1153-8. doi: 10.1002/bio.2879. Epub 2015 Mar 8.
Pyruvic acid and its derivatives occurring in most biological systems are known to exhibit several pharmacological properties, such as anti-inflammatory, neuroprotective or anticancer, many of which are suggested to originate from their antioxidant and free radical scavenger activity. The therapeutic potential of these compounds is a matter of particular interest, due to their mechanisms of action, particularly their possible antioxidant behaviour. Here, we report the results of a study of the effect of pyruvic acid (PA), ethyl pyruvate (EP) and sodium pyruvate (SP) on reactions generating reactive oxygen species (ROS), such as superoxide anion radicals, hydroxyl radicals and singlet oxygen, and their total antioxidant capacity. Chemiluminescence (CL) and spectrophotometry techniques were employed. The pyruvate analogues studied were found to inhibit the CL signal arising from superoxide anion radicals in a dose-dependent manner with IC50 = 0.0197 ± 0.002 mM for EP and IC50 = 69.2 ± 5.2 mM for PA. These compounds exhibited a dose-dependent decrease in the CL signal of the luminol + H2O2 system over the range 0.5-10 mM with IC50 values of 1.71 ± 0.12 mM for PA, 3.85 ± 0.21 mM for EP and 22.91 ± 1.21 mM for SP. Furthermore, these compounds also inhibited hydroxyl radical-dependent deoxyribose degradation in a dose-dependent manner over the range 0.5-200 mM, with IC50 values of 33.2 ± 0.3 mM for SP, 116.1 ± 6.2 mM for EP and 168.2 ± 6.2 mM for PA. All the examined compounds also showed antioxidant capacity when estimated using the ferric-ferrozine assay. The results suggest that the antioxidant activities of pyruvate derivatives may reflect a direct effect on scavenging ROS and, in part, be responsible for their pharmacological actions.
已知在大多数生物系统中存在的丙酮酸及其衍生物具有多种药理特性，如抗炎、神经保护或抗癌特性，其中许多特性被认为源于它们的抗氧化和自由基清除活性。由于这些化合物的作用机制，特别是其可能的抗氧化行为，它们的治疗潜力备受关注。在此，我们报告了一项关于丙酮酸（PA）、丙酮酸乙酯（EP）和丙酮酸钠（SP）对产生活性氧（ROS）的反应（如超氧阴离子自由基、羟基自由基和单线态氧）及其总抗氧化能力影响的研究结果。采用了化学发光（CL）和分光光度法技术。研究发现，所研究的丙酮酸类似物以剂量依赖性方式抑制超氧阴离子自由基产生的CL信号，EP的IC50 = 0.0197 ± 0.002 mM，PA的IC50 = 69.2 ± 5.2 mM。在0.5 - 10 mM范围内，这些化合物使鲁米诺 + H2O2系统的CL信号呈剂量依赖性降低，PA的IC50值为1.71 ± 0.12 mM，EP的IC50值为3.85 ± 0.21 mM，SP的IC50值为22.91 ± 1.21 mM。此外，这些化合物在0.5 - 200 mM范围内也以剂量依赖性方式抑制羟基自由基依赖性的脱氧核糖降解，SP的IC50值为33.2 ± 0.3 mM，EP的IC50值为116.1 ± 6.2 mM，PA的IC50值为168.2 ± 6.2 mM。当使用铁 - 亚铁嗪测定法评估时，所有检测的化合物也都显示出抗氧化能力。结果表明，丙酮酸衍生物的抗氧化活性可能反映了对清除ROS的直接作用，并且部分地解释了它们的药理作用。
