Molecular mechanisms of the nephroprotective action of polyphenols in experimental chronic kidney disease. Association with hydrogen sulfide system
Annotation. The results of a study of the effects of genistein, resveratrol and quercetin on the main markers of oxidative stress, thiol disulfide equilibrium and the state of the nitric oxide system in rat kidneys after modelling chronic kidney disease (CKD) (5/6 of a single kidney nephrectomy) is shown. Blood and single rat kidney homogenate were used for biochemical studies. Statistical processing of the obtained results was performed in the program “STATISTICA 6.1”. The results are presented as M±m. The significance of the difference between the scores was evaluated using the Student's t-test or the Mann-Whitney U-test. A nonparametric Spearman correlation coefficient was used to determine the correlation between two independent indicators. It was shown that the studied substances, especially quercetin, caused antioxidant activity in CKD, which was manifested by a significant decrease of MDA, CGP and NADPH oxidase activity (by 21.0–40.4%), as well as an increase in SOD activity (by 29.7–38.7%) in kidney compared with untreated animals. Reliable strong correlation (r=ǀ0.65–0.74ǀ) between the H2S content and oxidative stress markers was established. The use of polyphenols in CKD reduced the thiol-disulfide imbalance in rat kidneys: the activity of thioredoxin reductase significantly increased, the content of reduced thiol groups of proteins (by 16.0–66.4%) and the level of disulfides decreased (by 21.1–25.3%), in comparison with untreated animals. Stabilization of the thiol disulfide equilibrium is one of the mechanisms of the effect of polyphenols on the H2S system in the kidneys, since significant and strong correlation relationships were recorded between these indicators and the H2S content (r=ǀ0.63–0.75ǀ). The administration of resveratrol, and especially genistein, was accompanied by an increase in the activity of the eNOS (by 36.3–44.7%) and a decrease in the activity of iNOS (by 15.4–20.9%), in comparison with untreated animals. The NO system in the kidneys is an important molecular target for influence of genistein and resveratrol on the production of H2S during CKD is realized, since reliable strong correlation were recorded between the H2S content and the activity of NO synthase isoforms (r=ǀ0.70–0.75ǀ).
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