0000000001308407
AUTHOR
Liga Zvejniece
showing 18 related works from this author
The anti-inflammatory and antinociceptive effects of NF-κB inhibitory guanidine derivative ME10092
2010
The guanidine compound ME10092 (1-(3,4-dimethoxy-2-chlorobenzylideneamino)-guanidine) is known to possess anti-radical and anti-ischemic activity but its molecular targets have not been identified. This study investigated whether ME10092 regulates the nuclear factor kappa B (NF-kappaB)-mediated signal transduction in vivo. The effect of ME10092 treatment (1-100 pmol/mouse) on nuclear translocation of NF-kappaB, activation of expression of inflammatory mediators and production of nitric oxide were measured in the lipopolysaccharide (LPS)-induced brain inflammation model in mice in vivo. The antinociceptive activity of ME10092 was tested in the formalin-induced paw licking test. ME10092 dose-…
Skull Fractures Induce Neuroinflammation and Worsen Outcomes after Closed Head Injury in Mice
2020
The weight-drop model is used widely to replicate closed-head injuries in mice; however, the histopathological and functional outcomes may vary significantly between laboratories. Because skull fractures are reported to occur in this model, we aimed to evaluate whether these breaks may influence the variability of the weight-drop (WD) model. Male Swiss Webster mice underwent WD injury with either a 2 or 5 mm cone tip, and behavior was assessed at 2 h and 24 h thereafter using the neurological severity score. The expression of interleukin (IL)-6, IL-1β, tumor necrosis factor-α, matrix metalloproteinase-9, and tissue inhibitor of metalloproteinase-1 genes was m…
Functional Evaluation of THIQ, a Melanocortin 4 Receptor Agonist, in Models of Food Intake and Inflammation
2007
The central melanocortinergic system plays an important role in regulating different aspects of energy homeostasis and the immunomodulatory response. In the present study, we evaluated the in vivo activities of food intake suppression and anti-inflammatory activity of THIQ, which has been proposed to possess high and selective melanocortin-4 receptor agonistic activity in vitro. The results showed that THIQ (0.1, 0.3 and 1 nmol/rat, intracerebroventricularly) is less effective in reducing food intake and body weights of rats than the non-selective melanocortin receptor agonist melanotan II. Electron paramagnetic resonance measurements in mice brain tissue showed that THIQ at doses of 0.001 …
The differential influences of melanocortins on nociception in the formalin and tail flick tests
2006
Melanocortins exert multiple physiological effects that include the modulation of immune responses, inflammation processes, and pain transmission. In the present study we investigated the peripheral activity of natural melanocortins - alpha-, beta-, gamma1- and gamma2-melanocyte stimulating hormone (MSH) - and melanocortin receptor subtypes 3 and 4 (MC3/4 receptor) antagonist HS014 in pain (formalin and tail flick) tests after peptide subcutaneous administration in mice. In the formalin test, among all substances tested only alpha-MSH (1 micromol/kg) statistically significantly inhibited the formalin-induced first phase pain response, however, all tested peptides (except gamma1-MSH) at the …
The MC3 receptor binding affinity of melanocortins correlates with the nitric oxide production inhibition in mice brain inflammation model
2006
Melanocortins possess strong anti-inflammatory effects acting in the central nervous system via inhibition of the production of nitric oxide (NO) during brain inflammation. To shed more light into the role of melanocortin (MC) receptor subtypes involved we synthesized and evaluated some novel peptides, modified in the melanocyte-stimulating hormone (MSH) core structure, natural MCs and known MC receptor selective peptides - MS05, MS06. Since the study included both selective, high affinity binders and the novel peptides, it was possible to do the correlation analysis of binding activities and the NO induction-related anti-inflammatory effect of the peptides. beta-MSH, gamma1-MSH, gamma2-MSH…
Comparative pharmacological activity of optical isomers of phenibut
2007
Phenibut (3-phenyl-4-aminobutyric acid) is a GABA (gamma-aminobutyric acid)-mimetic psychotropic drug which is clinically used in its racemic form. The aim of the present study was to compare the effects of racemic phenibut and its optical isomers in pharmacological tests and GABAB receptor binding studies. In pharmacological tests of locomotor activity, antidepressant and pain effects, S-phenibut was inactive in doses up to 500 mg/kg. In contrast, R-phenibut turned out to be two times more potent than racemic phenibut in most of the tests. In the forced swimming test, at a dose of 100 mg/kg only R-phenibut significantly decreased immobility time. Both R-phenibut and racemic phenibut showed…
Effect of inhibiting carnitine biosynthesis on male rat sexual performance.
2008
l-carnitine has a documented role as a cofactor in cellular energy metabolism and fatty acid beta-oxidation pathways and it has also been considered to function in reproductive biology. We investigated whether decreasing concentrations of L-carnitine using an inhibitor of its biosynthesis, mildronate (3-(2,2,2-trimethylhydrazinium)-propionate), would influence the sexual behavior or sperm quality in male rats. Mildronate treatment induced a significant decrease in carnitine concentration and an increase in gamma-butyrobetaine (GBB) concentration in both plasma and testes extracts. However, the expression of carnitine palmitoyltransferase I in testes and testosterone concentration in plasma …
Synthesis, physicochemical characterization, cytotoxicity, antimicrobial, anti-inflammatory and psychotropic activity of new N-[1,3-(benzo)thiazol-2-…
2012
Abstract A series of new N-[(benzo)thiazol-2-yl]-2/3-[3,4-dihydroisoquinolin-2(1H)-yl]ethan/propanamide derivatives was synthesized and characterized by 1H, 13C NMR and IR spectroscopy and mass-spectrometry. A single crystal X-ray study of N-(1,3-benzothiazol-2-yl)-2-[3,4-dihydroisoquinolin-2(1H)-yl]ethanamide is reported to determine its conformational feature. The investigated compounds were found to be active in psychotropic in vivo, anti-inflammatory in vivo and cytotoxicity in vitro screening. They possess marked sedative action, reveal high anti-inflammatory activity, have selective cytotoxic effects and NO-induction ability concerning tumour cell lines. Some of the compounds synthesi…
Antidepressive-like Behavior-Related Metabolomic Signatures of Sigma-1 Receptor Knockout Mice
2022
Sigma-1 receptor (Sig1R) has been proposed as a therapeutic target for neurological, neu-rodegenerative, and psychiatric disorders, including depression and anxiety. Identifying metabolites that are affected by Sig1R absence and cross-referencing them with specific mood-related behaviors would be helpful for the development of new therapies for Sig1R-associated disorders. Here, we examined metabolic profiles in the blood and brains of male CD-1 background Sig1R knockout (KO) mice in adulthood and old age and correlated them with the assessment of depression-and anxiety-related behaviors. The most pronounced changes in the metabolic profile were observed in the plasma of adult Sig1R KO mice.…
Increased synthesis of nitric oxide in rat brain cortex due to halogenated volatile anesthetics confirmed by EPR spectroscopy
2002
Background: Halogenated volatile anesthetics (HVAs) are considered to be inhibitors of nitric oxide synthase (NOS). On other hand, NO mediates the vasodilation produced by HVAs. Thus, both increase and decrease of NO concentration in brain tissues are possible during anesthesia. Previously, we have observed an increase of NO content in rat brain cortex under halothane anesthesia. The goal of this study was to determine whether the observed phenomenon was general for this anesthetic group, if it was specific for brain cortex, and if the NO increase was due changes in NOS activity. Methods: NO scavengers were injected to adult rats 30 min prior to anesthesia. Rats were anesthetized by inhalat…
Beta-MSH inhibits brain inflammation via MC(3)/(4) receptors and impaired NF-kappaB signaling.
2005
The anti-inflammatory effects of melanocortin peptides have been demonstrated in different inflammation models. This is the first report describing the molecular mechanisms for the beta-MSH-induced suppression of bacterial lipopolisaccharide (LPS)-caused brain inflammation. We found that beta-MSH suppresses LPS-induced nuclear translocation of the transcription factor NF-kappaB, and inhibits the expression of inducible nitric oxide synthase, and the following nitric oxide overproduction in the brain, in vivo. Moreover, administering the preferentially MC(4) receptor selective antagonist HS014 blocked completely these effects, suggesting a tentative MC(4) receptor mediated mechanism of actio…
The cognition‐enhancing activity of E1R , a novel positive allosteric modulator of sigma‐1 receptors
2013
Background and Purpose Here, we describe the in vitro and in vivo effects of (4R,5S)-2-(5-methyl-2-oxo-4-phenyl-pyrrolidin-1-yl)-acetamide (E1R), a novel positive allosteric modulator of sigma-1 receptors. Experimental Approach E1R was tested for sigma receptor binding activity in a [3H](+)-pentazocine assay, in bradykinin (BK)-induced intracellular Ca2+ concentration ([Ca2+]i) assays and in an electrically stimulated rat vas deferens model. E1R's effects on cognitive function were tested using passive avoidance (PA) and Y-maze tests in mice. A selective sigma-1 receptor antagonist (NE-100), was used to study the involvement of the sigma-1 receptor in the effects of E1R. The open-field test…
Investigation into Stereoselective Pharmacological Activity of Phenotropil
2011
Phenotropil (N-carbamoylmethyl-4-aryl-2-pyrrolidone (2-(2-oxo-4-phenyl-pyrrolidin-1-yl) acetamide; carphedon)) is clinically used in its racemic form as a nootropic drug that improves physical condition and cognition. The aim of this study was to compare the stereoselective pharmacological activity of R- and S-enantiomers of phenotropil in different behavioural tests. Racemic phenotropil and its enantiomers were tested for locomotor, antidepressant and memory-improving activity and influence on the central nervous system (CNS) using general pharmacological tests in mice. After a single administration, the amount of compound in brain tissue extracts was determined using an ultra performance …
Beta- and gamma-melanocortins inhibit lipopolysaccharide induced nitric oxide production in mice brain.
2003
The pro-opiomelanocortin-derived peptide alpha-melanocyte stimulating hormone (alpha-MSH) mediates many diverse physiological actions, including anti-inflammatory and immunomodulatory effects. However, little is known about the physiological roles of the other melanocortins, beta- and gamma-MSH. Here, we investigated the effects of melanocortin peptides in an in vivo neuroinflammation model. Six hours following intracisternal (i.c.) administration of 10 microg lipopolysaccharide (LPS) to mice a five-fold increase in the nitric oxide (NO) level was seen in the animals' brains, when detected by electron paramagnetic resonance (EPR). All tested melanocortins, alpha-, beta-, gamma1- and gamma2-…
The sensorimotor and cognitive deficits in rats following 90- and 120-min transient occlusion of the middle cerebral artery
2012
Middle cerebral artery occlusion (MCAO) is the most commonly used method to study the neurological and histological outcomes and the pathological mechanisms of ischaemic stroke. The current work compares sensorimotor and cognitive deficits and the infarct volume in rats following a transient 90- or 120-min MCAO, which allows the appropriate behavioural tests to be chosen based on the goal and design of the experiment. In the beam-walking test, we found significant differences between the 90- and 120-min MCAO groups in the number of foot faults made with the impaired hindlimb on post-stroke days 3, 7 and 14. In the cylinder test, a difference between the 90- and 120-min groups was observed o…
Mildronate treatment improves functional recovery following middle cerebral artery occlusion in rats
2011
Mildronate (3-(2,2,2-trimethylhydrazinium) propionate) is an inhibitor of l-carnitine biosynthesis and an anti-ischemic drug. In the present study, we investigated the effects of mildronate in rats following focal cerebral ischemia. Male Wistar rats were subjected to transient occlusion of the middle cerebral artery (MCAO) for 90min, followed by the intraperitoneal administration of mildronate at doses of 100 and 200mg/kg 2h after reperfusion and then daily for an additional 14days. The beam-walking, rota-rod and cylinder tests were used to assess sensorimotor function, and vibrissae-evoked forelimb-placing and limb-placing tests examined responses to tactile and proprioceptive stimulation.…
Genetic inactivation of the sigma-1 chaperone protein results in decreased expression of the R2 subunit of the GABA-B receptor and increased suscepti…
2021
There is a growing body of evidence demonstrating the significant involvement of the sigma-1 chaperone protein in the modulation of seizures. Several sigma-1 receptor (Sig1R) ligands have been demonstrated to regulate the seizure threshold in acute and chronic seizure models. However, the mechanism by which Sig1R modulates the excitatory and inhibitory pathways in the brain has not been elucidated. The aim of this study was to compare the susceptibility to seizures of wild type (WT) and Sig1R knockout (Sig1R−/−) mice in intravenous pentylenetetrazol (PTZ) and (+)-bicuculline (BIC) infusion-induced acute seizure and Sig1R antagonist NE-100-induced seizure models. To determine pos…
CCDC 907303: Experimental Crystal Structure Determination
2014
Related Article: Alla Zablotskaya, Izolda Segal, Athina Geronikaki, Tatiana Eremkina, Sergey Belyakov, Marina Petrova, Irina Shestakova, Liga Zvejniece, Vizma Nikolajeva|2013|Eur.J.Med.Chem.|70|846|doi:10.1016/j.ejmech.2013.10.008