Effect of Peroxiredoxin 6 on Nephrons in the Early Reperfusion Period After Renal Ischemia in Rats
DOI:
https://doi.org/10.37482/2687-1491-Z130Keywords:
renal ischemia-reperfusion, morphofunctional changes in nephrons, peroxiredoxins, urea, creatinine, kidney injury molecule-1 (KIM-1)Abstract
Renal reperfusion injury develops rapidly after ischemia relief. It is with the onset of reperfusion that a cascade of pathological processes is launched, which means that measures to protect the kidney have to be taken as early as in this period. The aim of the paper was to study the effect of exogenous peroxiredoxin 6 (Prx6) on the morphofunctional state of nephrons in the initial reperfusion period following ischemia. Materials and methods. The right kidney of rats was subjected to 45-minute ischemia with prior left-sided nephrectomy and examined after 2, 5 and 24 hours of reperfusion. Exogenous Prx6 was administered intravenously 15 minutes before ischemia. Results. The research showed that nephrectomy has no effect on the morphology of a single kidney, but leads to an increase in urea and creatinine in the blood within 24 hours. We noted signs of morphological and functional damage to nephrons after 2 hours of reperfusion, which tend to increase in the course of 24 hours. In addition, we observed a rise in blood creatinine and urea concentrations, an increase in the areas of renal corpuscles, glomeruli, and Bowman’s capsule, as well as dystrophic changes in nephrocytes and an increase in the immunosignal area of the kidney injury molecule-1 (KIM-1). When exogenous Prx6 was used, we observed normalization of the size of nephron components, a decrease in KIM-1 immunosignal and an improvement in the kidney’s excretory function both in the early reperfusion period and after 24 hours. Thus, exogenous Prx6 reduces damage to nephrons during the early reperfusion period, which improves their compensatory and adaptive properties in ischemia-reperfusion injury.
Downloads
References
Plotnikov E.Y., Kazachenko A.V., Vyssokikh M.Y., Vasileva A.K., Tcvirkun D.V., Isaev N.K., Kirpatovsky V.I., Zorov D.B. The Role of Mitochondria in Oxidative and Nitrosative Stress During Ischemia/Reperfusion in the Rat Kidney // Kidney Int. 2007. Vol. 72, № 12. P. 1493–1502. DOI: 10.1038/sj.ki.5002568
Шарапов М.Г., Гордеева А.Е., Гончаров Р.Г., Тихонова И.В., Равин В.К., Темнов А.А., Феcенко Е.Е., Новоселов В.И. Влияние экзогенного пероксиредоксина 6 на состояние мезентеральных сосудов и тонкого кишечника при ишемически-реперфузионном поражении // Биофизика. 2017. Т. 62, вып. 6. С. 1208–1220.
Goncharov R.G., Rogov K.A., Temnov A.A., Novoselov V.I., Sharapov M.G. Protective Role of Exogenous Recombinant Peroxiredoxin 6 Under Ischemia-Reperfusion Injury of Kidney // Cell Tissue Res. 2019. Vol. 378, № 2. P. 319–332. DOI: 10.1007/s00441-019-03073-z
Granger D.N., Kvietys P.R. Reperfusion Injury and Reactive Oxygen Species: The Evolution of a Concept // Redox Biol. 2015. № 6. P. 524–551. DOI: 10.1016/j.redox.2015.08.020
Yingzhong C., Lin C., Chunbin W. Clinical Effects of Cyclosporine A on Reperfusion Injury in Myocardial Infarction: A Meta-Analysis of Randomized Controlled Trials // SpringerPlus. 2016. Vol. 5, № 1. Art. № 1117. DOI: 10.1186/s40064-016-2751-y
Valasani K.R., Sun Q., Fang D., Zhang Z., Yu Q., Guo Y., Li J., Roy A., ShiDu Yan S. Identification of a Small Molecule Cyclophilin D Inhibitor for Rescuing Aβ-Mediated Mitochondrial Dysfunction // ACS Med. Chem. Lett. 2016. Vol. 7, № 3. P. 294–299. DOI: 10.1021/acsmedchemlett.5b00451
Sharapov M.G., Glushkova O.V., Parfenyuk S.B., Gudkov S.V., Lunin S.M., Novoselova E.G. The Role of TLR4/ NF-κB Signaling in the Radioprotective Effects of Exogenous Prdx6 // Arch. Biochem. Biophys. 2021. Vol. 702. Art. № 108830. DOI: 10.1016/j.abb.2021.108830
Turovsky E.A., Varlamova E.G., Plotnikov E.Y. Mechanisms Underlying the Protective Effect of the Peroxiredoxin-6 Are Mediated via the Protection of Astrocytes During Ischemia/Reoxygenation // Int. J. Mol. Sci. 2021. Vol. 22, № 16. Art. № 8805. DOI: 10.3390/ijms22168805
Mu R., Ye S., Lin R., Li Y., Guo X., An L. Effects of Peroxiredoxin 6 and Its Mutants on the Isoproterenol Induced Myocardial Injury in H9C2 Cells and Rats // Oxid. Med. Cell. Longev. 2022. Vol. 2022. Art. no. 2576310. DOI: 10.1155/2022/2576310
Юлдашев А.Ю., Рахманов Р.Р., Юлдашев А.А., Таринова М.В. Гистофизиология поверхностных и юкстамедуллярных сосудистых клубочков почек после острой массивной кровопотери // Нефрология. 2007. Т. 11, № 2. С. 68–71.
Чиниева М.И. Морфологические изменения структур канальцевой и сосудистой систем почек при белковой нагрузке // Арх. внутр. медицины. 2018. Т. 8, № 3. С. 219–222. DOI: 10.20514/2226-6704-2018-8-3-219-222
Lee Y.J. Knockout Mouse Models for Peroxiredoxins // Antioxidants. 2020. Vol. 9, № 2. Art. № 182. DOI: 10.3390/antiox9020182
Li L., Yu A.-Q. The Functional Role of Peroxiredoxin 3 in Reactive Oxygen Species, Apoptosis, and Chemoresistance of Cancer Cells // J. Cancer Res. Clin. Oncol. 2015. Vol. 141, № 12. P. 2071–2077. DOI: 10.1007/s00432-015-1916-3
Bonventre J.V. Kidney Injury Molecule-1: A Translation Journey // Trans. Am. Clin. Climatol. Assoc. 2014. Vol. 125. P. 293–299.
