EFFECTS OF AGMATINE AND RED WINE CONCENTRATE, ENRICHED WITH POLYPHENOLIC COMPOUNDS, ON L-ARGININE / NITROGEN OXIDE SYSTEM IN THE BRAIN OF RATS WITH EXPERIMENTAL DIABETES MELLITUS

Biol. Stud. 2021; 15(2): 25–34 • DOI: https://doi.org/10.30970/sbi.1502.655

K. R. Spryn, M. V. Sabadashka, N. O. Sybirna


DOI: http://dx.doi.org/10.30970/sbi.1502.655

Abstract


Background. Diabetes mellitus is a chronic endocrine metabolic disease with absolute or relative insufficiency of insulin, accompanied by impaired metabolism. Endogenous bioamine agmatine may become a basis of new antidiabetic drugs, as it is capable to induce the release of some peptide hormones, in particular insulin, and can regulate NO synthesis. Natural polyphenols are potential multifunctional agents that also can reduce the risk of diabetes and diabetic complications. The aim of the study was to evaluate the effect of agmatine and red wine concentrate, enriched with polyphenolic compounds, on NO-synthase activity and the content of NO stable metabolites under experimental diabetes mellitus.
Materials and Methods. The experiments were conducted on white Wistar male rats. Diabetes was induced by intra-abdominal injection of streptozotocin. From the 14th day after the induction of diabetes, agmatine was injected intramuscularly or red wine concentrate, enriched with polyphenolic compounds was administrated orally to animals for 14 days. Rats were decapitated under ether anesthesia on the 28th day of the experiment. In the brain of rats, the activity of constitutive (Ca2+-dependent) and inducible (Ca2+-independent) isoforms of NO-synthase and the content of nitrite and nitrate anions were determined.
Results and Discussion. The activities of constitutive and inducible isoforms of NO-synthase were increased in the brain of diabetic rats. The administration of both agmatine and red wine concentrate, enriched with polyphenolic compounds, caused the reduction of the activities of NO-synthase isoforms. In the case of diabetes, the administration of agmatine contributes to the increase of nitrite and nitrate content in brain cells compared to diabetes. The administration of red wine concentrate, enriched with polyphenolic compounds, also promotes nitrite levels but does not affect the nitrate level.
Conclusion. We found that the red wine concentrate, enriched with polyphenolic compounds, has a stronger effect on the activity of Ca2+-dependent and Ca2+-independent isoforms of NO-synthase, as well as the content of nitrites and nitrates in brain of rats with experimental diabetes mellitus, compared to the effect of agmatine.

Keywords: agmatine, red wine concentrate, polyphenolic compounds, diabetes mellitus, NO-synthase, nitrite anions, nitrate anions

 

Received 15 May, 2021  ●  Revision 28 May, 2021  ●  Accepted 02 June, 2021  ●  Published 30 June, 2021

 


Full Text:

PDF

References


1. Afonin A.A, Drucker N.A., Gunko V.O., Loginova I.G., Afonina T.A. Agmatin: spectrum of acti­vity in the brain, the diagnostic and therapeutic potential in central nervous system diseases. Modern Problems of Science and Education, 2018; 4: 1-11. (In Russian)
CrossrefGoogle Scholar

2. Arndt M.A., Battaglia V., Parisi E. et al. The arginine metabolite agmatine protects mitochondrial function and conferse resistance to cellular apoptosis. American Journal of Physiology-Cell Physiology, 2009; 296(6): 1411-1419.
CrossrefPubMedPMCGoogle Scholar

3. Bahadoran Z., Mirmiran P., Azizi F. Dietary polyphenols as potential nutraceuticals in management of diabetes: a review. Journal of Diabetes & Metabolic Disorders, 2013; 12(1): 43.
CrossrefPubMedPMCGoogle Scholar

4. Bhat N.R., Feinstein D.L., Shen Q., Bhat A.N. p38 MAPK-mediated transcriptional activation of inducible nitric-oxide synthase in glial cells. Journal of Biological Chemistry, 2002; 277(33): 29584-29592.
CrossrefPubMed ● PMC ● Google Scholar

5. Dawson J.A., Knowles R.G. A microtiter-plate assay of nitric oxide synthase activity. Molecular Biotechnology, 1999; 12: 275-279.
CrossrefGoogle Scholar

6. Donertas B., Unel C.C., Erol K. Cannabinoids and agmatine as potential therapeutic alternatives for cisplatin-induced peripheral neuropathy. Journal of Experimental Pharmacology, 2018; 10: 19-28.
CrossrefPubMedPMCGoogle Scholar

7. Drel V.R. The main mechanisms of occurrence and development of diabetic complications: the role of nitrative stress. Studia Biologica, 2010; 4(2): 141-158. (In Ukrainian)
CrossrefGoogle Scholar

8. Fairbanks C.A., Schreiber K.L., Brewer K.L. et al. Agmatine reverses pain induced by inflammation, neuropathy, and spinal cord injury. Proceedings of the National Academy of Sciences, 2000; 97(19): 10584-10589.
CrossrefPubMedPMCGoogle Scholar

9. Galea E., Regunathan S., Eliopoulos V., Feinstein D.L., Reis D.J. Inhibition of mammalian nitric oxide synthases by agmatine, an endogenous polyamine formed by decarboxylation of arginine. Biochemical Journal, 1996; 316(1): 247-249.
CrossrefPubMedPMCGoogle Scholar

10. Halsted C.H. Dietary supplements and functional foods: 2 sides of a coin? The American Journal of Clinical Nutrition, 2003; 77(4): 1001S-1007S.
CrossrefPubMedGoogle Scholar

11. Knowles R.G., Moncada S. Nitric oxide synthases in mammals. Biochemical Journal, 1994; 298(2): 249-258.
CrossrefPubMedPMCGoogle Scholar

12. Lorenz M., Wessler S., Follmann E. et al. A constituent of green tea, epigallocatechin-3-gallate, activates endothelial nitric oxide synthase by a phosphatidylinositol-3-OH-kinase-, cAMP-dependent protein kinase-, and Akt-dependent pathway and leads to endothelial-dependent vasorelaxation. Journal of Biological Chemistry, 2004, 279(7): 6190-6195.
CrossrefPubMedGoogle Scholar

13. Lowry O.H., Rosebrough, Farr A.L., Randal R.J. Protein measurement with the Folin phenol reagent. Journal of Biological Chemistry, 1951; 193(1): 265-275.
CrossrefGoogle Scholar

14. Maltsev A.V. Agmatine modulates calcium handling in cardiomyocytes of hibernating ground squirrels through calcium-sensing receptor signaling. Cellular Signaling, 2018; 51: 1-12.
CrossrefPubMedGoogle Scholar

15. Miranda K.M., Espey M.G., Wink D.A. A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide, 2001; 5(1): 62-71.
CrossrefPubMedGoogle Scholar

16. Naumenko V.G., Phakadze O.G., Sakalo O.A. Find the keys to diabetes control! Kyiv: Triumph, 2004. 64 p. (In Ukrainian)

17. Önal A., Delen Y., Ülker S., Soykan N. Agmatine attenuates neuropathic pain in rats: Possible mediation of nitric oxide and noradrenergic activity in the brainstem and cerebellum. Life Sciences, 2003; 73(4): 413-428.
CrossrefGoogle Scholar

18. Piletz J.E., Aricioglu F., Cheng J.T. et al. Agmatine: clinical applications after 100 years in translation. Drug Discov Today, 2013; 18(17-18): 880-893.
CrossrefPubMedGoogle Scholar

19. Rasines-Perea Z., Teissedre P.-L. Grape Polyphenols' Effects in Human Cardiovascular Diseases and Diabetes. Molecules, 2017; 22(1): 68.
CrossrefPubMedPMCGoogle Scholar

20. Rosenberg M.L., Tohidi V., Sherwood K., Gayen S., Medel R., Gilad G.M. Evidence for dietary agmatine sulfate efectiveness in neuropathies associated with painful small fiber neuropathy. A pilot open-label consecutive case series study. Nutrients, 2020; 12: 576-585.
CrossrefPubMedPMCGoogle Scholar

21. Sener A., Lebrun F., Blaicher F., Malaisse W.J. Stimulus-secretion coupling of arginine-induced insulin release: Insulinotro action of agmatine. Biochemical Pharmacology, 1989; 38(2): 327-330.
CrossrefGoogle Scholar

22. Sinnreich M., Taylor B.V., Dyck P.J. Diabetic neuropathies. The Neurologist, 2005; 11(2): 63-79.
CrossrefPubMedGoogle Scholar

23. Stoclet J.-C., Chataigneau T., Ndiaye M., Oak M.-H., El Bedoui J., Chataigneau M., Schini-Kerth V.B. Vascular protection by dietary polyphenols. European Journal of Pharmacology, 2004; 500(1-3): 299-313.
CrossrefPubMedGoogle Scholar

24. Sun C., Zhao C., Guven E. C. et al. Dietary polyphenols as antidiabetic agents: Advances and opportunities. Food Frontiers, 2020; 1(1): 18-44.
CrossrefGoogle Scholar

25. Sutherland B.A., Rahman R.M., Appleton I. Mechanisms of action of green tea catechins, with a focus on ischemia-induced neurodegeneration. The Journal of Nutritional Biochemistry, 2006; 17(5): 291-306.
CrossrefPubMedGoogle Scholar

26. Sybirna N.O., Datsyuk L.O., Datsyuk U.V. Pat. U201313977 Ukraine. Method of preparation of red wine natural polyphenolic complex concentrate. Applicant LNU І. Franko; Appl. 2.02.2013. 5 p. (Publication decision 26.02.2014). (In Ukrainian)

27. Vafeiadou K., Vauzour D., Lee H.Y., Rodriguez-Mateos A., Williams R.J., Spencer J.P. The citrus flavanone naringenin inhibits inflammatory signalling in glial cells and protects against neuroinflammatory injury. Archives of Biochemistry and Biophysics, 2009; 484(1): 100-109.
CrossrefPubMedGoogle Scholar

28. Wang X., Chen S., Ma G., Ye M., Lu G. Genistein protects dopaminergic neurons by inhibiting microglial activation. NeuroReport, 2005; 16(3): 267-270.
CrossrefPubMedGoogle Scholar


Refbacks

  • There are currently no refbacks.


Copyright (c) 2021 K. R. Spryn, M. V. Sabadashka, N. O. Sybirna

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.