Molecular mechanisms of the nephroprotective action of polyphenols in experimental chronic kidney disease. Association with hydrogen sulfide system


  • S.A. Konjuch National Pirogov Memorial Medical University, Vinnytsya, Ukraine
  • N.I. Voloshchuk National Pirogov Memorial Medical University, Vinnytsya, Ukraine
  • A.V. Melnyk National Pirogov Memorial Medical University, Vinnytsya, Ukraine
  • O.M. Denysiuk National Pirogov Memorial Medical University, Vinnytsya, Ukraine
  • P.V. Zhorniak National Pirogov Memorial Medical University, Vinnytsya, Ukraine
Keywords: genistein, resveratrol, quercetin, hydrogen sulfide, chronic kidney disease, rats.

Abstract

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).

References

1. Verevkina, I. V. Tochilkin, A. I., Popova, N. A. (1977). Kolorimetricheskij metod opredeleniya SH-grupp i S-S-svyazej v belkakh pri pomoshhi 5,5'-ditiobis(2-nitrobenzojnoj kisloty`) kisloty` [Colorimetric method for determining SH-groups and S-S-bonds in proteins using 5.5’-dithiobis (2-nitrobenzoic acid) acid]. V Orekhovich V. N. (red.). Sovremenny`e metody` v biokhimii [Modern methods in biochemistry].. M.: Mediczina.

2. Vladimirov, Yu. V., & Archakov, A. I. (1972). Perekisnoe okislenie lipidov v biologicheskikh membranakh [Lipid peroxidarion in biological membranes]. M.: Nauka.

3. Gula, N. M., Kosyakova, G. V., & Berdishev, A. G. (2007). Vpliv N-stearoyiletanolami`nu na NO-sintaznij shlyakh generaczi`yi oksidu azotu v aorti` ta serczi` shhuri`v i`z streptozotoczini`ndukovanim di`abetom [Effect of N-Stearoylethanolamine on NO Synthesis of Nitric Oxide Generation in Aorta and Heart of Rats with Streptozotocin-Induced Diabetes]. Ukrayins`kij bi`okhi`mi`chnij zhurnal – Ukrainian Biochemical Journal, 79(5), 153–158.

4. Korenman, I. M. (1975). Metody` opredeleniya organicheskikh soedinenij [Methods for determining of organic compounds]. M.: Khimiya.

5. Kostyuk, V. A., Potapovich, A. I., & Kovaleva, Zh. V. (1990). Prostoj i chuvstvitel`ny`j metod opredeleniya aktivnosti superoksiddismutazy`, osnovanny`j na reakczii okisleniya kverczitina [A Simple and Sensitive Method for Determining Superoxide Dismutase Activity Based on Quercitin Oxidation Reaction]. Voprosy` mediczinskoj khimii – Medical chemistry issues, 2, 88–89.

6. Kochetov, G. A. (1980). Prakticheskoe rukovodstvo po e`nzimologii [Practical Guide to Enzymology]. Moskva: Vy`sshaya shkola.

7. Shevchuk, S. V., Pentiuk, O. O., Musin, R. A., & Zaichko, N. V. (2003). Sposib vyznachennia karbonilnykh spoluk v syrovattsi krovi. Patent Ukrainy na vynakhid №58110A, MPK 7 A61K35/16. № 2002107890. Kyiv: Derzhavne patentne vidomstvo Ukrainy [Method for determination of carbonyl compounds in serum. Patent of Ukraine for invention No. 58110A, IPC 7 A61K35 / 16. No. 2002107890. Kiev: State Patent Office of Ukraine.].

8. Strygol, S. Yu., Lisoviy, V. M., Zupanets, І. А., Shebeko, S. К., Maslova, N. F., Gozenko, А. І. ... Kharchenko, D. S. (2009) Metody eksperymentalʹnoho urazhennya nyrok dlya farmakolohichnykh doslidzhenʹ [Methods of experimental renal involvement for pharmacological studies]. Metodieskie rekomendaczii – Guidelines. Kiyiv, 36.

9. Altaany, Z., Yang, G., & Wang, R. (2013). Crosstalk between hydrogen sulfide and nitric oxide in endothelial cells. J. Cell Mol. Med., 17(7), 879–888. doi: 10.1111/jcmm.12077.

10. Filipovic, M. R., Miljkovic, J. L., Nauser, T., Royzen, M., Klos, K., Shubina, T. … Ivanović-Burmazović, I. (2012). Chemical characterization of the smallest S-nitrosothiol, HSNO; cellular cross-talk of H2S and S-nitrosothiols. J. Am. Chem. Soc., 134(29), 12016–1227. doi: 10.1021/ja3009693.

11. Fukui, T., Ishizaka, N., Rajagopalan, S., Laursen, J. B., Capers, Q., Taylor, W. R. … Griendling, K. K. (1997). p22phox mRNA expression and NADPH oxidase activity are increased in aortas from hypertensive rats. Circ. Res., 80(1), 45–51.

12. Kimura, H. (2017). Hydrogen Sulfide and Polysulfide Signaling. Antioxid Redox Signal., 27(10), 619–621. doi: 10.1089/ars.2017.7076.

13. Kopecká, J., Krijt, J., Raková, K., & Kožich, V. (2011). Restoring assembly and activity of cystathionine β-synthase mutants by ligands and chemical chaperones. J. Inherit. Metab. Dis., 34(1), 39–48. doi: 10.1007/s10545-010-9087-5.

14. Stein, A., & Bailey, Sh. M. (2013). Redox biology of hydrogen sulfide: Implications for physiology, pathophysiology, and pharmacology. Redox Biology, 1, 32–39. doi: 10.1016/j.redox.2012.11.006.

15. Wiliński, B., Wiliński, J., Somogyi, E., Piotrowska, J., & Góralska, M. (2011). Amlodipine affects endogenous hydrogen sulfide tissue concentrations in different mouse organs. Folia Med. Cracov., 51(1–4), 29–35. Retrieved from https://www.researchgate.net/publication/230670023_Amlodipine_affects_endogenous_hydrogen_sulfide_tissue_concentrations_in_different_mouse_organs.

Zaichko, N. V., Melnik, A. V., Yoltukhivskyy, M. M., Olhovskiy, A. S., & Palamarchuk, I. V. (2014). Hydrogen sulfide: metabolism, biological and medical role. Ukr. Biochem. J., 86(5), 5–25.
Published
2019-12-30
How to Cite
Konjuch, S., Voloshchuk, N., Melnyk, A., Denysiuk, O., & Zhorniak, P. (2019). Molecular mechanisms of the nephroprotective action of polyphenols in experimental chronic kidney disease. Association with hydrogen sulfide system. Reports of Vinnytsia National Medical University, 23(4), 561-566. https://doi.org/https://doi.org/10.31393/reports-vnmedical-2019-23(4)-01