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
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.