AUTHOR=Strutynska Nataliіa , Goshovska Yulia , Mys Lidiia , Strutynskyi Ruslan , Luchkova Alina , Fedichkina Raisa , Okhai Iryna , Korkach Yuliia , Sagach Vadym 

TITLE=Glutathione restores the mitochondrial redox status and improves the function of the cardiovascular system in old rats

JOURNAL=Frontiers in Physiology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2022.1093388

DOI=10.3389/fphys.2022.1093388

ISSN=1664-042X

ABSTRACT=<p><bold>Introduction:</bold> Aging is accompanied by cardiovascular disorders which is associated with an imbalance of pro- and antioxidant systems, the mitochondrial dysfunction, etc. Glutathione (GSH) plays a critical role in protecting cells from oxidative damage. The aim of the work was to study the effect of exogenous glutathione on the redox status of mitochondria, the content of H<sub>2</sub>S and the function of the cardiovascular system in old rats.</p><p><bold>Methods:</bold> Experiments were performed on adult (6 months) and old (24 months) Wistar rats divided into three groups: adult, old and glutathionetreated old rats. Glutathione was injected intraperitoneally at a dose of 52 mg/kg. We investigated glutathione redox balance, H<sub>2</sub>S levels, oxidative stress, the opening of the mitochondrial permeability transition pore (mPTP), the resistance of isolated heart to ischemia/reperfusion in Langendorff model, endothelium-dependent vasorelaxation of isolated aortic rings, and cardiac levels of <italic>3-MST</italic>, <italic>CSE</italic>, and <italic>UCP3</italic> mRNA were determined using real-time PCR analysis.</p><p><bold>Results:</bold> Our data shows that in old rats treated with glutathione, the balance of its oxidized and reduced form changes in the direction of a significant increase (by 53.6%) of the reduced form. Glutathione pretreatment significantly increased the H<sub>2</sub>S levels, mtNOS activity, and <italic>UCP3</italic> expression which considered as protective protein, and conversely, significantly decreased oxidative stress markers (the rate of O<sub>2</sub>•<sup>−</sup> generation, the levels of H<sub>2</sub>O<sub>2</sub>, diene conjugates and malone dialdehyde, in 2.5, 2.3, 2, and 1.6 times, respectively) in heart mitochondria. This was associated with the inhibition mitochondrial permeability transition pore opening and increased resistance of the isolated heart to ischemia/reperfusion in these animals. At the same time, in glutathione-treated old rats, we also observed restoration of endothelium-dependent vasorelaxation responses to acetylcholine, which were almost completely abolished by the NO-synthase inhibitor L-NAME.</p><p><bold>Conclusion:</bold> Thus, the pretreatment of old rats with glutathione restores the mitochondrial redox status and improves the function of the cardiovascular system.</p>