Comparative Study of Protective Action of Exogenous 2-Cys Peroxiredoxins (Prx1 and Prx2) Under Renal Ischemia-Reperfusion Injury.

Mars G Sharapov,Vladimir I Novoselov,Ruslan G Goncharov,Valery V Boyarintsev,Gleb I Filkov,Alexander V Trofimenko

doi:10.3390/antiox9080680

Mars G Sharapov, Vladimir I Novoselov + Show 4 more

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https://doi.org/10.3390/antiox9080680

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Abstract

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.

Highlights

It is currently well known that ischemia-reperfusion (I/R) injury is a key factor in the development of many pathological conditions, including various socially significant diseases: myocardial infarction, ischemic stroke, acute renal failure, etc. [1,2,3,4]
In addition to the antioxidant activity, the time of the presence of exogenous Prx1 and Prx2 in the in the kidneys during I/R damage plays an important role in their protective effect
According to all criteria under consideration, Prx1 is approximately 15–20% more effective than Prx2, which may be due to its higher enzymatic activity, because the peroxidase activity of Prx1 in vitro is about 20–30% higher than that of Prx2

Summary

Introduction

It is currently well known that ischemia-reperfusion (I/R) injury is a key factor in the development of many pathological conditions, including various socially significant diseases: myocardial infarction, ischemic stroke, acute renal failure, etc. [1,2,3,4]. Malperfusion (ischemia) leads to a rapid development of pathological processes, including a decrease in ATP level, suppression of aerobic metabolism and switching of the cell to anaerobic processes, which provokes accumulation of lactate, acidification of the cell microenvironment, activation of endogenous oxidases (NADPH oxidase, monoamine oxidase, glycerophosphate dehydrogenase, etc.) [5,6]. All these processes result in deterioration of the structural and functional integrity of ischemic tissues. The use of IPC can be implemented through both physiological (for example, short-term pre-ischemia) and pharmacological (drugs that cause hypoxia, respiratory uncoupling in mitochondria, glycogen synthase kinase (GSK) inhibitors, etc.) manipulations [9,10]

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