This review is dedicated to the role of nitration of proteins by tyrosine residues in physiological and pathological conditions. First of all, we analyze the biochemical evidence of peroxynitrite formation and reactions that lead to its formation, types of posttranslational modifications (PTMs) induced by reactive nitrogen species, as well as three biological pathways of tyrosine nitration. Then, we describe two possible mechanisms of protein nitration that are involved in intracellular signal transduction, as well as its interconnection with phosphorylation/dephosphorylation of tyrosine. Next part of the review is dedicated to the role of proteins nitration in different pathological conditions. In this section, special attention is devoted to the role of nitration in changes of functional properties of actin—protein that undergoes PTMs both in normal and pathological conditions. Overall, this review is devoted to the main features of protein nitration by tyrosine residue and the role of this process in intracellular signal transduction in basal and pathological conditions.

BackgroundAn impaired leukocytes function is the factor causing the susceptibility of patients with diabetes mellitus to infections. The outmost importance for the understanding of the immunological processes involved in diabetes pathogenesis is to give the characteritics of the immunological profile and changes therein, during the course of desease. Long-used in folk medicine to treat diabetes Galega officinalis L. has been chosen for the correction of the immune system dysfunction.MethodsThe experiments were conducted on male Wistar rats. Fractionation of bone marrow cells suspension was performed in a three-layer ficoll–sodium amidotrizoate density gradient. The lymphocytic-granulocytic cells proliferative activity was studied using enzyme immunoassay with 5-bromo-2′-deoxyuridine (BrdU). For staining of bone marrow preparations May-Gruenwald-Romanowsky-Giemsa (Pappenheim) method was used. To evaluate the content of cationic proteins and myeloperoxidase in neutrophilic leukocytes cytochemical studies were performed. Content of tumor necrosis factor alpha was carried out by immuno-enzymatic analysis. Lymphocytes apoptosis was examined by fluorescent analysis using annexin V.ResultsDiabetes mellitus development was accompanied with violation of neutrophils and lymphocytes proliferation, increased activity of myeloperoxidase and enhanced apoptosis process. Administration of Galega officinalis extract under the condition of diabetes promotes the restoration of neutrophils bone marrow pool and the reduction of lymphoblasts number and causes inhibition of the lymphocytes apoptosis process.ConclusionsInvestigated medicine has a pronounced immunocorrective effect under the conditions of diabetes mellitus and can become the basis for creating a new generation of antidiabetic drugs.

Hypoglycemic and antioxidant properties of extracts of medicinal plants Galega officinalis L. (aboveground part) and yacon (Smallanthus sonchifolius Poepp. & Endl.) (leaves) as potential sources of biologically active substances with antidiabetic action have been studied. The pronounced hypoglycemic effect of Galega officinalis extract, devoid of alkaloids, at a dose of 600 mg/kg in experimental diabetes mellitus (DM) has been proven. The established effect is evidenced by a decrease in the concentration of glucose and glycosylated hemoglobin in the blood, increase glucose tolerance of cells, increase C-peptide and insulin content in the plasma of rats’ blood. The effective hypoglycemic effect of the extract in the studied pathology was confirmed by histological examination of the pancreas. The cytoprotective effect of the studied extract on pancreatic cells at a dose of 1200 mg/kg was experimentally confirmed. In the standard cut area, an increase was found in the number of Langerhans islets, their average area, diameter, volume, and a number of β-cells relative to these indicators in animals with diabetes. Comparative screening of the antioxidant properties of 30, 50, 70, and 96% water–ethanol extracts of yacon indicates the highest potential of 50% water-ethanol extract to block free radicals in in vitro model experiments. The non-alkaloid fraction of Galega officinalis extract showed moderate antioxidant activity and was inferior to yacon extract in its ability to neutralize reactive oxygen species (ROS) and bind metal ions of variable valence. The level of antioxidant potential of the studied extracts is due to differences in the quantitative content of compounds of phenolic nature in their compositions. The obtained data on the biological effects of Galega officinalis extract on the structural and functional state of β-cells of the pancreas and antioxidant properties of Galega officinalis and yacon extracts substantiate the prospects of using these plants to create antidiabetic medicines and functional foods based on them.

Under diabetes mellitus, the administration of Galega officinalis promotes restoration of leukocyte precursors' bone marrow pool and normalizes their proliferative activity. This plant protects the functional state of leukocytes by modulating actin cytoskeleton formation and through quantitative redistribution of leukocyte membrane glycoconjugates. Galega officinalis prevents the development of diabetesassociated oxidative stress which results in antiapoptotic activity. The normalization of leukocytes' proliferative and functional capacity by Galega officinalis, along with its antiapoptotic and hypoglycemic effects, can improve the course of the disease and may prevent the development of complications of diabetes.

Introduction. Metabolic syndrome is a cluster of metabolic abnormalities that includes hypertension, central obesity, insulin resistance and atherogenic dyslipidemia. Given the wide geographical distribution and growing number of people suffering from this disease, there is an urgent need in developing animal models that would accurately reproduce the development of all symptoms of human metabolic syndrome (insulin resistance, dyslipidemia, obesity and hypertension). The most cost-effective method related to the real causes of metabolic syndrome is the use of different types of diets. Materials and Methods. The study was performed on white outbred male rats about 6 months old and weighing 300–400 g. The metabolic syndrome was induced by high-fat and high-carbohydrate diets. The lipid-enriched diet involved the consumption of regular chow diet for laboratory animals with additional fat content (40 % by weight of chow). The source of additional lipids was olive oil, which is rich in monounsaturated fatty acids (MUFAs). Animals on the diet enriched in carbohydrates together with regular chow diet for laboratory animals consumed 10 % fructose solution instead of drinking water. Glucose tolerance tests were conducted and areas under the glycemic curves were calculated. We determined the content of glycated hemoglobin and glucose concent­ration, the concentration of low-density lipoproteins (LDL), high-density lipoproteins (HDL), triglycerides and cholesterol in the blood plasma of rats. Results. The development of metabolic syndrome induced by an excessive consumption of carbohydrates and lipids for 42 days was accompanied by impaired glucose tolerance, increased glycosylated hemoglobin, triglycerides and cholesterol concentrations, as well as a decreased HDL content. An increase in the concentrations of LDL and activity of paraoxonase were found due to the induction of the pathological condition by an excessive fat intake, while a high carbohydrate diet caused a decrease in paraoxonase activity. Conclusions. The use of fructose for 42 days causes the most pronounced manifestations of the studied pathology. The use of this model will allow determining the biochemical and molecular changes that accompany the development of this pathological condition. It will also facilitate the development and evaluation of the effectiveness of new therapeutic approaches to the treatment of metabolic syndrome.