The Protective Effect of a Chimeric PSH Antioxidant Enzyme in Renal Ischemia–Reperfusion Injury

Abstract

Abstract—A rapid increase in the concentration of free radicals and reactive oxygen species at the reperfusion stage is the most dangerous stage of ischemia–reperfusion injury. An avalanche-like increase in the level of reactive oxygen species and secondary products of free radical oxidation of biological macromolecules leads to the development of oxidative stress. The use of exogenous antioxidants can reduce the concentration of reactive oxygen species in the affected tissues and suppress or correct the course of oxidative stress; thus, it significantly reduces the severity of ischemia–reperfusion injury. Acute ischemic renal failure is one of the most important social problems in a comprehensive list of pathologies associated with ischemia–reperfusion. The nephroprotective effect of a chimeric PSH antioxidant enzyme that includes human peroxiredoxin 6 and Mn-containing superoxide dismutase of Escherichia coli has been shown on an animal model of bilateral ischemia–reperfusion renal injury. The recombinant chimeric PSH protein was able to neutralize a maximally possible wide range of reactive oxygen species due to the superoxide dismutase and peroxidase activities. It has been shown with histological, biochemical, and molecular biological methods that the preliminary administration of the chimeric PSH protein before ischemia–reperfusion significantly reduced the degree of renal tissue injury and led to a quick normalization of their structural and functional state. In addition, the administration of the PSH enzyme increased the survival of experimental animals by a factor of more than 1.5. The use of the recombinant chimeric PSH enzyme can be an effective approach in the prevention and treatment of renal ischemia–reperfusion injury, as well as for maintaining an isolated kidney during transplantation.