Shen Yan-Cheng, Shen Yan-Jhih, Lee Wen-Sen, Chen Michael Yu-Chih, Tu Wei-Chia, Yang Kun-Ta
Ph.D. Program in Pharmacology and Toxicology, School of Medicine, Tzu Chi University, Hualien 97004, Taiwan.
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
Antioxidants (Basel). 2021 Oct 22;10(11):1667. doi: 10.3390/antiox10111667.
To identify the core structure of 2-aminoethoxydiphenyl borate (2-APB) responsible for the anti-oxidative and protective effect on the ischemia/reperfusion (I/R)-induced heart injury, various 2-APB analogues were analyzed, and several antioxidant assays were performed. Cell viability was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Myocardial infarct size was quantified using triphenyl tetrazolium chloride (TTC) staining. The levels of tumor necrosis factor-alpha (TNF-α) and cleaved-caspase-3 protein were evaluated as an indicator for the anti-inflammatory and anti-apoptotic effect, respectively. Our data show that 2-APB, diphenylborinic anhydride (DPBA) and 3-(diphenylphosphino)-1-propylamine (DP3A) all exerted the anti-oxidative activity, but only 2-APB and DPBA can scavenge HO. 2-APB and DPBA can potently inhibit hydrogen peroxide (HO)- and hypoxanthine/xanthine oxidase (HX/XOD)-induced increases in intracellular HO and H9c2 cell death. 2-APB and DPBA were able to decrease the I/R-induced adult rat cardiomyocytes death, myocardial infarct size, and the levels of malondialdehyde (MDA) and creatine kinase-MB (CK-MB). Our results suggest that the two benzene rings with a boron atom comprise the core structure of 2-APB responsible for the anti-oxidative effect mediated through the reaction with HO and generation of phenolic compounds, which in turn reduced the I/R-induced oxidative stress and injury in the rat heart.
为了确定2-氨基乙氧基二苯基硼酸酯（2-APB）对缺血/再灌注（I/R）诱导的心脏损伤具有抗氧化和保护作用的核心结构，对各种2-APB类似物进行了分析，并进行了多种抗氧化试验。使用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）试验测定细胞活力。使用氯化三苯基四氮唑（TTC）染色对心肌梗死面积进行定量。分别评估肿瘤坏死因子-α（TNF-α）和裂解的半胱天冬酶-3蛋白水平，作为抗炎和抗凋亡作用的指标。我们的数据表明，2-APB、二苯基硼酸酐（DPBA）和3-(二苯基膦基)-1-丙胺（DP3A）均具有抗氧化活性，但只有2-APB和DPBA能够清除羟基自由基（HO）。2-APB和DPBA能够有效抑制过氧化氢（HO）和次黄嘌呤/黄嘌呤氧化酶（HX/XOD）诱导的细胞内HO增加以及H9c2细胞死亡。2-APB和DPBA能够减少I/R诱导的成年大鼠心肌细胞死亡、心肌梗死面积以及丙二醛（MDA）和肌酸激酶-MB（CK-MB）水平。我们的结果表明，带有硼原子的两个苯环构成了2-APB的核心结构，该结构通过与HO反应并生成酚类化合物介导抗氧化作用，进而减轻了I/R诱导的大鼠心脏氧化应激和损伤。
