Analgesic Activity of the Low Molecular Weight Neurotrophin-3 Dipeptide Mimetic GTS-301.

It was previously shown that the original dipeptide mimetic of the 4th loop of neurotrophin-3 (NT-3) hexamethylenediamide bis-(N-monosuccinyl-L-asparaginyl-L-asparagine) (GTS-301), like the full-length neurotrophin, predominantly activates the tyrosine kinase receptor TrkC and has a neuroprotective effect in vitro at concentrations of 10-10 M, as well as antidiabetic (0.1 and 0.5 mg/kg) and antidepressant (5 and 10 mg/kg) effects after systemic administration in rodents.

Antigenotoxic Activity of Polyphenolic Composition BP-C2 in Mouse Germ Cells In Vivo.

In vivo antigenotoxic activity of BP-C2 composition (at doses of 60, 80, and 120 mg/kg) based on polyphenolic compounds derived from hydrolyzed lignin was evaluated in mouse germ cells. The BP-C2 composition dose-dependently reduced the aneugenic activity of topoisomerase II inhibitor etoposide in mouse oocytes without affecting the clastogenic activity of the genotoxicant. In mouse testicular cells, the BP-C2 composition reduced the DNA-damaging activity of the pro-oxidant genotoxicant dioxidine, but not etoposide.

Enhancement of the Clastogenic Effects of Topotecan In Vivo by Tyrosyl-DNA Phosphodiesterase 1 Inhibitors.

Topotecan administered intraperitoneally at single doses of 0.25, 0.5, and 1 mg/kg induced chromosomal aberrations in bone marrow cells of F(CBA×C57BL/6) hybrid mice in a dose-dependent manner.

Low-Affinity NMDA Receptor Antagonist Hemantane in a Topical Formulation Attenuates Arthritis Induced by Freund's Complete Adjuvant in Rats.

Purpose: N-methyl-D-aspartate (NMDA) receptors that are expressed by T-cells modulate T-cell proliferation, cytotoxicity and cell migration toward chemokines. Several studies have shown an anti-inflammatory effect of NMDA receptor antagonists. This study compares the effect of the noncompetitive low-affinity NMDA receptor antagonist N-(2-adamantyl)-hexamethyleneimine hydrochloride (hemantane) in a topical formulation (gel) with the cyclooxygenase (COX) inhibitor diclofenac in a topical formulation (gel) in rats with arthritis induced by Freund's Complete Adjuvant (FCA).

Effect of Polyphenolic Composition BP-C2 on Lung Carcinogenesis Induced by Urethane in Progeny of Irradiated Male BALB/c Mice.

We studied the effects of polyphenolic composition BP-C2, comprising molybdenum with lignin derivatives, on lung carcinogenesis induced by urethane in the progeny of F male BALB/c mice preconceptionally exposed to radiation in a dose of 1 Gy. The multiplicity of lung tumors in the progeny of irradiated mice was higher than in the progeny of non-irradiated male parents by 50% in females and 43% in males (p<0.05).

Chronic Ethanol Consumption by Rats before Mating Affects Working Memory in the Offspring.

Parameters of non-spatial and spatial memory were evaluated in sexually mature offspring of outbred rats (females and males F0) consuming a 10% ethanol solution for 30 weeks before mating. We found a significant increase in the recognition index in F1 males and its decrease in F1 females in the novel object recognition test. During the first days of the experiment in T-maze, a decrease in spatial memory was revealed in F1 males, which remained at the trend level until the end of testing; no significant deviations were detected in F1 females.

Damage to Nuclear and Mitochondrial DNA in Different Organs in Streptozotocin-Induced Diabetes Models in BALB/c Mice.

Male BALB/c mice with streptozotocin-induced diabetes mellitus were used to study nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) damage using comet DNA assay and real-time PCR, respectively. In animals receiving single injection of streptozotocin in a dose of 200 mg/kg, severe hyperglycemia was observed on days 10 and 21 of the experiment, while after 5-fold administration of streptozotocin in a dose of 40 mg/kg, it developed on days 14 and 28. DNA damage and the level of atypical DNA comets in the liver increased both on days 10 and 21 after single administration of streptozotocin, and on days 14 and 28 after repeated administrations.

Antigenotoxic and antimutagenic effects of lignin derivative BP-C2 against dioxidine and cyclophosphamide in vivo in murine cells.

The study investigated antigenotoxic and antimutagenic activity of novel lignin-derived polyphenolic composition (BP-C2) with ammonium molybdate towards cyclophosphamide and dioxidine in the bone marrow, blood and liver cells of BALB/c mice. BP-C2 was given to mice via gavage at 60, 80 and 120 mg/kg once 1 h before single intraperitoneal injection of a genotoxic agent. 1.

[Genotoxicity of psychotropic drugs in experimental and clinical studies].

The analysis of experimental data on the study of the genotoxic activity of psychotropic drugs published over the past 25 years has been carried out. It has been shown that the information describing the genotoxicity of psychotropic drugs is characterized by fragmentation, contradictions, and the conditions for their experimental production often do not meet modern requirements. Conclusions about the presence or absence of genotoxic properties can be made only for 9.

Low-Molecular-Weight Mimetic of BDNF Loop 2 Reduces Ethanol Consumption in Female Rats.

The study examined the effect of GTS-201, a low-molecular weight mimetic of brain-derived neurotrophic factor (BDNF) loop 2, on persistent alcohol craving in outbred male and female albino rats with ethanol preference score ~50% developed in the free choice paradigm between 10% ethanol and water over 24 weeks. Both single and subchronic (5 days) injections of GTS-201 in a daily dose of 5 μg/kg reduced alcohol deprivation effect in female, but not in male rats. The possibility of in vivo sex-dependent regulation of modeled alcohol craving with a low-molecular-weight dipeptide mimetic of BDNF loop 2 was demonstrated and sex-related differences in this effect were revealed.

Induced Cell Death as a Possible Pathway of Antimutagenic Action.

The existing concepts of antimutagenesis are briefly reviewed. Published reports on antimutagenic and proapoptotic properties of some polyphenols and compounds of other chemical groups obtained in representative in vitro and in vivo experiments on eukaryotic test systems are discussed. The relationships between the antimutagenic and proapoptotic properties of the analyzed compounds (naringin, apigenin, resveratrol, curcumin, N-acetylcysteine, etc.

Angiogenic Effects of Anxiolytic Fabomotizole.

In vitro experiments performed on an isolated human endothelial HUVEC cell culture showed that the anxiolytic fabomotizole, which, in addition to the anxiolytic effect, has neuroprotective and cardioprotective activities largely associated with its agonistic action on sigma-1 receptors and shows a pronounced angiogenic activity. Fabomotizole angiogenic activity is realized in the range concentration from 10 to 10 M and is doze-dependent. In the literature, data on the presence of angiogenic activity in sigma receptor agonists have not been previously reported.

Experimental Evaluation of Anxiolytic and Analgesic Properties of a New Linear Methoxyphenyltriazaalkane Derivative with Cardiotropic Activity.

The anxiolytic and analgesic properties of compound ALM-802, a cardiotropic linear methoxyphenyltriazaalkane derivative, combining pharmacophore elements of p-FOX inhibitors trimetazidine and ranolazine were studied in vivo. In the elevated plus-maze test, ALM-802 after acute intraperitoneal administration in doses of 1-8 mg/kg dose-dependently prevented the development of anxiety in BALB/c mice. Chronic intraperitoneal administration of ALM-802 in a dose of 2 mg/kg to alcohol-preferring rats attenuated anxiogenesis induced by ethanol withdrawal.

Effects of 5-Hydroxypyrimidine Derivatives on Tumor Growth and Lifespan of C57BL/6 Mice with Epidermoid Lung Carcinoma.

The effects of 5-hydroxypyrimidine derivatives SNK-411 (2-isobutyl-4,6-dimethyl-5-hydroxypyrimidine) and SNK-578 (2-isobutyl-4,6-dimethyl-5-hydroxypyrimidine chlorohydrate) on the tumor growth and survival of male C57BL/6 mice with transplanted Lewis lung epidermoid carcinoma (LLC) were studied in animals receiving intraperitoneal treatment on days 2-15 of tumor development. Compound SNK-578 in a dose of 10 mg/kg significantly inhibited tumor growth (by 3.6 times; 72.

Comet assay on one- and two-cell mouse embryos.

DNA damage quantified as the comet tail length was assessed using in vitro and in vivo comet assay on one- and two-cell mouse embryos obtained by natural mating. The use of a protocol with three layers of agarose reduces the embryo loss and makes it possible to study a small number of embryos. A significantly lower level of basal, but not induced DNA damage was found in embryos with cleaved zona pellucida compared to embryos with intact zona pellucida.

Genotoxicity of cationic lipopeptide nanoparticles.

The genotoxicity of cationic lipopeptide nanoparticles (cLPNPs) was evaluated in vivo and in vitro comet assay and the in vivo chromosome aberrations test. In vitro comet assay, human blood cells were exposed to cLPNPs at the concentration of 2.5, 5, 10, 20, 40 and 100 μg/mL.

Alterations in the nigrostriatal system following conditional inactivation of α-synuclein in neurons of adult and aging mice.

The etiology and pathogenesis of Parkinson's disease (PD) are tightly linked to the gain-of-function of α-synuclein. However, gradual accumulation of α-synuclein aggregates in dopaminergic neurons of substantia nigra pars compacta (SNpc) leads to the depletion of the functional pool of soluble α-synuclein, and therefore, creates loss-of-function conditions, particularly in presynaptic terminals of these neurons. Studies of how this late-onset depletion of a protein involved in many important steps of neurotransmission contributes to PD progression and particularly, to worsening the nigrostriatal pathology at late stages of the disease are limited and obtained data, are controversial.

Neuroprotective Dipeptide Noopept Prevents DNA Damage in Mice with Modeled Prediabetes.

In experiments on BALB/c mice, prediabetes was modeled by administration of streptozotocin in a dose of 130 mg/kg. DNA damage was assessed by the method of DNA comets. Noopept (0.

A Translational Model of Chronic Heart Failure.

We created a translational model of chronic heart failure in rats that developed in 3 months after reproducing experimental anterior transmural myocardial infarction. The model simulated the basic clinicodiagnostic criteria of this disease: impaired contractility and dilatation of heart ventricles, signs of venous congestion, elevated plasma content of biochemical markers, and abnormal overexpression of AT1aR and β-adrenoceptors.

Selank, Peptide Analogue of Tuftsin, Protects Against Ethanol-Induced Memory Impairment by Regulating of BDNF Content in the Hippocampus and Prefrontal Cortex in Rats.

The effects of a peptide anxiolytic Selank synthesized on the basis of the endogenous peptide tuftsin on memory impairment and content of brain-derived neurotrophic factor (BDNF) in brain structures were analyzed in outbred rats receiving 10% ethanol as the only source of fluid for 30 weeks. In the object recognition test, Selank (0.3 mg/kg a day, 7 days, intraperitoneally) produced a cognitive-stimulating effect in 9 months rats not exposed to ethanol (p<0.

Evaluation of Kagocel Genotoxicity.

Antiviral drug Kagocel in concentrations of 0.0008, 0.004, 0.

Neuroprotective Lithium Salts Protect Pancreatic β-Сells from Damage.

We studied antidiabetic effects and cytoprotective activity of two lithium salts (lithium chloride and lithium carbonate) on the model of streptozotocin-induced diabetes mellitus type 2 in Wistar rats. Using the method of β-cells detection with antibodies to insulin, we demonstrated that streptozotocin reduced the number of β-cells and impaired their morphological structure. Both lithium preparations administered to diabetic animals for 28 days in doses of 10 and 8.

Alcoholic Cardiomyopathy: Translation Model.

We developed a translation model of alcoholic cardiomyopathy in rats. By the end of forced alcoholization (the rats received 10% ethanol solution as the only source of fluid for 24 weeks; mean daily ethanol consumption was 5.0-6.

Induced Aneugenic Effects in Mouse Oocytes In Vivo.

Aneugenic effects of the chemicals with antitumor activity were studied in mouse oocytes in vivo by cytogenetic analysis. In control mice, no oocytes with numerical chromosome aberrations were found. Colchicine (0.

Genotoxicity of two new carbazole derivatives with antifungal activity.

The class of carbazoles includes compounds with high biological activities and broad spectra of action. PLX01107 and PLX01008 are xenomycins, a new subclass of antimicrobial carbazole derivatives demonstrating strong antifungal activity in vitro. We performed three tests, a bacterial reverse mutation assay (Ames test), in vitro cytokinesis-block micronucleus assay, and chromosome aberration test in mouse bone marrow cells, to investigate the possible genotoxicity of these compounds.