Browsing by Author "Dzirkale, Zane"

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    Comparative study of taurine and tauropyrone : GABA receptor binding, mitochondrial processes and behaviour
    (2011-02) Dzirkale, Zane; Pupure, Jolanta; Rumaks, Juris; Svirskis, Simons; Vanina, Marija; Mezhapuke, Rudolfs; Sile, Velga; Fernandes, Maria Augusta; Duburs, Gunars; Klusa, Vija
    Objectives Taurine, a sulfur-containing amino acid, has high hydrophilicity and is poorly absorbed. Tauropyrone, a taurine-containing 1,4-dihydropyridine derivative, is suggested to have greater activity than taurine owing to improved physicochemical properties that facilitate delivery of the compound to target cells. The aim of this study was to determine whether the 1,4-dihydropyridine moiety in tauropyrone improves the pharmacological efficacy of taurine in vitro and in vivo. Methods The effects of taurine and tauropyrone, as well as of the 1,4-dihydropyridine moiety were compared in in-vitro experiments to determine the binding to GABA receptors and influence on mitochondrial processes (isolated rat liver mitochondria), and in in-vivo tests to assess the influence on behavioural effects caused by the GABA-A receptor ligands, bicuculline, diazepam and ethanol. Key findings Unlike taurine, tauropyrone did not display binding activity for the GABA-A receptor, and only taurine (but not tauropyrone) at low doses (0.1, 1.0 and 10 mg/kg) antagonised the bicuculline-induced convulsion effect. Taurine and tauropyrone had no effect on diazepam myorelaxing action, and they both exerted a comparable 'anti-ethanol' effect (shortening of the ethanol-sleeping time). Taurine and tauropyrone did not influence processes of mitochondrial bioenergetics. Conclusions The action of tauropyrone at the level of the GABA-A receptor differs qualitatively from that of taurine, probably because of its 1,4-dihydropyridine moiety, which may hinder access to the GABA-A receptor GABA site. Tauropyrone does not show improved pharmacological efficacy in in-vitro and in-vivo studies in comparison with taurine.
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    Evaluation of "stress relief" dietary supplement on animal stress level and locomotion
    (2018) Svirskis, Šimons; Klimaviciusa, Linda; Dzirkale, Zane; Institute of Microbiology and Virology
    Search of new approaches for harmless, non-medication treatment of body dysfunctions is still on the agenda of vet and human practitioners and researchers as well. This study presents evaluation of the effect of "Stress Relief" dietary supplement (SR) on mice behaviour under different acute short-term stress conditions and treatment duration. Five experiments were performed and in each 40 animals were randomly split into four (I-IV) groups, where I and II - non-stressed mice, III and IV - stressed animals, I and III received water with trace mineral solution (TMS), II and IV received water with SR. As stress factors, forced swimming, rodent predator odour or both together were applied. Locomotor activity under normal and stress conditions in Open Field were observed and measured by a SMART video-tracking system. Blood glucose level was measured as well. SR showed a reversal of stress-decreased locomotor activity in all stress models - distance walked increased almost twice (p < 0.0001), central zone crossings and time spent in it were 2-4 times greater than in the control group (p < 0.0001 and p = 0.0002, respectively), and fast movement episodes and maximal speed increased by 50-200%. In addition, complete normalisation of stress-induced elevation of blood glucose level (p < 0.0001) was noted. These results demonstrate for the first time that the effect of "Stress Relief" formula (water additives-minerals processed by know-how way in Vital Force Technology using Dr. Yury Kronn method) can be observed in laboratory animals, and that the effects are significant and repeatable. SR shows fear- and stress-reducing activity, which does not sufficiently differ between 7-, 9-, 14-, 28- and 32-day treatment regimes.
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    Mildronate and its Neuroregulatory Mechanisms : Targeting the Mitochondria, Neuroinflammation, and Protein Expression
    (2013-08-04) Beitnere, Ulrika; Pupure, Jolanta; Isajevs, Sergejs; Rumaks, Juris; Svirskis, Simons; Dzirkale, Zane; Kalvinsh, Ivars
    This review for the first time summarizes the data obtained in the neuropharmacological studies of mildronate, a drug previously known as a cardioprotective agent. In different animal models of neurotoxicity and neurodegenerative diseases, we demonstrated its neuroprotecting activity. By the use of immunohistochemical methods and Western blot analysis, as well as some selected behavioral tests, the new mechanisms of mildronate have been demonstrated: a regulatory effect on mitochondrial processes and on the expression of nerve cell proteins, which are involved in cell survival, functioning, and inflammation processes. Particular attention is paid to the capability of mildronate to stimulate learning and memory and to the expression of neuronal proteins involved in synaptic plasticity and adult neurogenesis. These properties can be useful in neurological practice to protect and treat neurological disorders, particularly those associated with neurodegeneration and a decline in cognitive functions.
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    Neuroprotective properties of mildronate, a small molecule, in a rat model of parkinson's disease
    (2010-11) Klusa, Vija Z.; Isajevs, Sergejs; Svirina, Darja; Pupure, Jolanta; Beitnere, Ulrika; Rumaks, Juris; Svirskis, Simons; Jansone, Baiba; Dzirkale, Zane; Muceniece, Ruta; Kalvinsh, Ivars; Vinters, Harry V.
    Previously, we have found that mildronate [3-(2,2,2-trimethylhydrazinium) propionate dihydrate], a small molecule with charged nitrogen and oxygen atoms, protects mitochondrial metabolism that is altered by inhibitors of complex I and has neuroprotective effects in an azidothymidine-neurotoxicity mouse model. In the present study, we investigated the effects of mildronate in a rat model of Parkinson's disease (PD) that was generated via a unilateral intrastriatal injection of the neurotoxin 6-hydroxydopamine (6-OHDA). We assessed the expression of cell biomarkers that are involved in signaling cascades and provide neural and glial integration: the neuronal marker TH (tyrosine hydroxylase); ubiquitin (a regulatory peptide involved in the ubiquitin-proteasome degradation system); Notch-3 (a marker of progenitor cells); IBA-1 (a marker of microglial cells); glial fibrillary acidic protein, GFAP (a marker of astrocytes); and inducible nitric oxide synthase, iNOS (a marker of inflammation). The data show that in the 6-OHDA-lesioned striatum, mildronate completely prevented the loss of TH, stimulated Notch-3 expression and decreased the expression of ubiquitin, GFAP and iNOS. These results provide evidence for the ability of mildronate to control the expression of an array of cellular proteins and, thus, impart multi-faceted homeostaticmechanisms in neurons and glial cells in a rat model of PD. We suggest that the use of mildronate provides a protective effect during the early stages of PD that can delay or halt the progression of this neurodegenerative disease.