Sharapov Mars G, Goncharov Ruslan G, Filkov Gleb I, Trofimenko Alexander V, Boyarintsev Valery V, Novoselov Vladimir I
Laboratory of Mechanisms of Reception, Institute of Cell Biophysics of the Russian Academy of Sciences, PSCBR RAS, 142290 Pushchino, Moscow Region, Russia.
Faculty of Biological and Medical Physics, Laboratory of Special Medical Equipment, Technology and Pharmaceuticals, Moscow Institute of Physics and Technology (MIPT), 141701 Dolgoprudny, Moscow Region, Russia.
Antioxidants (Basel). 2020 Jul 29;9(8):680. doi: 10.3390/antiox9080680.
The pathogenesis of ischemia-reperfusion (I/R) injuries is based on oxidative stress caused by a sharp increase in the concentration of free radicals, reactive oxygen species (ROS) and secondary products of free radical oxidation of biological macromolecules during reperfusion. Application of exogenous antioxidants lowers the level of ROS in the affected tissues, suppresses or adjusts the course of oxidative stress, thereby substantially reducing the severity of I/R injury. We believe that the use of antioxidant enzymes may be the most promising line of effort since they possess higher efficiency than low molecular weight antioxidants. Among antioxidant enzymes, of great interest are peroxiredoxins (Prx1-6) which reduce a wide range of organic and inorganic peroxide substrates. In an animal model of bilateral I/R injury of kidneys (using histological, biochemical, and molecular biological methods) it was shown that intravenous administration of recombinant typical 2-Cys peroxiredoxins (Prx1 and Prx2) effectively reduces the severity of I/R damage, contributing to the normalization of the structural and functional state of the kidneys and an almost 2-fold increase in the survival of experimental animals. The use of recombinant Prx1 or Prx2 can be an efficient approach for the prevention and treatment of renal I/R injury.
缺血再灌注(I/R)损伤的发病机制基于再灌注期间自由基、活性氧(ROS)浓度急剧增加以及生物大分子自由基氧化的次级产物所引起的氧化应激。应用外源性抗氧化剂可降低受影响组织中的ROS水平,抑制或调节氧化应激过程,从而大幅减轻I/R损伤的严重程度。我们认为,使用抗氧化酶可能是最具前景的研究方向,因为它们比低分子量抗氧化剂具有更高的效率。在抗氧化酶中,过氧化物还原酶(Prx1-6)备受关注,它们能还原多种有机和无机过氧化物底物。在双侧肾脏I/R损伤的动物模型中(采用组织学、生物化学和分子生物学方法),研究表明静脉注射重组典型2-半胱氨酸过氧化物还原酶(Prx1和Prx2)可有效减轻I/R损伤的严重程度,有助于使肾脏的结构和功能状态恢复正常,并使实验动物的存活率提高近2倍。使用重组Prx1或Prx2可能是预防和治疗肾脏I/R损伤的有效方法。