N. A. Bondarenko

Nitric oxide as a factor of genetically determined resistance to stress damages and adaptive protection.

August rats are more resistant to stress-induced gastric damages than Wistar rats. These interstrain differences were abolished after blockade of nitric oxide (NO) synthesis with NO-synthase inhibitor L-NNA, which indicates that NO contributes to genetically determined resistance to stress-induced injuries. Repeated treatment with L-NNA caused gastric ulceration in Wistar, but not in August rats. This is probably related to higher basal production and more intensive accumulation of NO in August rats compared to Wistar rats. Administration of L-NNA during adaptation to hypoxia suppressed its protective effects on the stomach in stress, which indicates that NO acts as the factor of adaptive protection.

Proliferation, Migration, and Production of Nitric Oxide by Bone Marrow Multipotent Mesenchymal Stromal Cells from Wistar Rats in Hypoxia and Hyperglycemia

We studied proliferation, migration, and secretion of NO by bone marrow multipotent mesenchymal stromal cells from Wistar rats during conditioning under hypoxic and hyperglycemic conditions and the effect of erythropoietin on these parameters. A stimulating effect of erythropoietin on cell proliferation under normal conditions and activation of cell proliferation under conditions of hypoxia and hyperglycemia were demonstrated. Erythropoietin abolishes suppression of cell proliferation in culture with normal glucose level under conditions of H2O2-induced hypoxia, while under conditions of hyperglycemia, inhibition of cell proliferation becomes more pronounced. Hypoxia promotes activation of cell migration along the growth factor concentration gradient and addition of erythropoietin to the nutrient medium leads to a decrease in cell migration activity. Erythropoietin stimulates NO production by cells cultured under the conditions of hypoxia and hyperglycemia.

Antistress Effect of Nitric Oxide

Rat strains feature different resistances to stress. The increased production of nitric oxide (NO) in the August strain prevents the appearance of ulcerous lesions of gastric mucosa and behavioral changes induced by restraint stress. Wistar rats feature a lower level of NO production and are more sensitive to restraint stress compared to the August rats according to both the ulcerous gastric lesions and behavioral parameters. The stress-induced release of catecholamines was mimicked by experimental hyperfunction of the dopaminergic (DA) system induced by L-DOPA. The NO synthase inhibitor Nω-nitro-L-arginine (L-NNA) enhanced the L-DOPA-induced behavioral changes. This effect was more pronounced in the August strain. The administration of the exogenous NO donor, dinitrosyl iron complexes (DNIC), limited the behavioral disturbances induced by L-DOPA in both rat strains. The protective effect of DNIC in conditions of the DA system hyperfunction is similar to the effect of a D2blocker sulpiride. Thus, NO has a central antistress effect apparently mediated by limiting the release of catecholamines.

Effect of Vascular Endothelial Growth Factor and Erythropoietin on Functional Activity of Fibroblasts and Multipotent Mesenchymal Stromal Cells

The study examined the effect of VEGF and erythropoietin on proliferative and migratory activities of skin fibroblasts and multipotent mesenchymal stromal cells of human adipose tissue. VEGF stimulated proliferation and migration of fi broblasts, but produced no significant effect on functional activity of multipotent mesenchymal stem cells. Erythropoietin stimulated proliferation of both cell types, but did not affect their migration.

Comparative Effects of Platelet-Rich Plasma, Platelet Lysate, and Fetal Calf Serum on Mesenchymal Stem Cells

We studied the effects of human platelet-rich plasma and platelet lysate on proliferation, migration, and colony-forming properties of rat mesenchymal stem cells. Platelet-rich plasma and platelet lysate stimulated the proliferation, migration, and colony formation of mesenchymal stem cells. A real-time study showed that platelet-rich plasma produces the most potent stimulatory effect, while both platelet-rich plasma and platelet lysate stimulated migration of cells.

Antiproliferative Potential of Officinal Forms and Nanoparticles of Lithium Salts.

We studied the effect of officinal forms and nanoparticles of lithium carbonate and lithium citrate on proliferative activity of hepatoma-29 cells. Lithium carbonate nanoparticles suppressed proliferation of hepatoma-29 cells in lower concentrations than officinal form of this salt. The antiproliferative effect of lithium salts i activation of apoptosis and arrest of hepatoma-29 cells in the G2/M phase of the cell cycle.

Cholinopositive effect of dilept (neurotensin peptidomimetic) as the basis of its mnemotropic effect.

Dilept eliminated learning disturbances in the extrapolation avoidance test, caused by chronic injections of scopolamine alone and in combination with madopar to rats. Dilept improved the dynamics of training and parameters of spatial memory impaired by olfactory bulbectomy (operation causing hypofunction of the central cholinergic system). The detected choline-positive effect of dilept together with pronounced dopaminergic activity necessitate its further development as a drug effective in positive and negative symptoms of schizophrenia and psychotic manifestations of Alzheimer’s disease.

Neuromodulatory Mechanism Underlying the Effect of the Atypical Dipeptide Neuroleptic Dilept

We studied the effects of a new dipeptide neuroleptic Dilept (N-caproyl-L-prolyl-L-tyrosine methyl ester) on activity of neurotransmitter systems in the brain. Dilept possessed antidopamine, glutamate modulatory, and cholinomimetic properties. These data indicate that Dilept is of potential efficacy in relieving positive and negative symptoms of schizophrenia.

Behavioral peculiarities and reactions of brain dopaminergic systems in rats with different resistance to acute hypobaric hypoxia

Locomotor activity in the open field test did not correlate with rat resistance to acute hypobaric hypoxia; there was a correlation between this resistance and rat behavior during acute stress. Immobility was characteristic of rats with low and particularly medium resistance to hypoxia; this reaction can be abolished by antidepressants. By contrast, highly resistant rats were mainly hyperactive. The resistance to hypoxia was associated with extreme parameters of dopaminergic neuron functioning. In low-resistant rats locomotor stereotypia was maximal, while perioral stereotypia was the minimal; highly resistant rats were characterized by an opposite pattern, and medium-resistant rats occupied an intermediate position.

Differences in Behavioral Patterns and Resistance to Stress-Induced Gastric Ulceration between August and Wistar Rats Adapted and Unadapted to Hypoxia

The incidence of gastric ulceration induced by acute emotional stress in Wistar rats is 3 times higher than in August rats, and the mean number of gastric ulcers in Wistar rats 6.3-fold surpassed that in August rats. Wistar rats predisposed to stress-induced ulceration displayed suppressed locomotor and exploratory activities in the open field test, while August rats had more stable behavioral patterns and enhanced exploratory activity after stress. Short-term preadaptation to hypobaric hypoxia for 6 days attenuated stress-induced gastric ulceration, whereas long-term adaptation (40 days) aggravated the severity of gastric ulcers in August and Wistar rats. The interstrain differences in stress-induced ulceration persisted after adaptation. The data suggest that these differences are related to genetically determined peculiarities of production and metabolism of NO and glucocorticoids in August and Wistar rats.