A method of measuring of glutathione peroxidase activity using HO was adapted for homogenates of murine brains. If the amount of reduced glutathione was at the constant level of 0.55 mM, the concentration of HO of 0.192 mM was saturating for glutathione peroxidase of murine brain and was selected as an optimal concentration for the estimation of enzyme activity in tris-HCl buffer with addition of NaN and EDTA (pH 8.5) at the incubation temperature of 37°C. The homogenates were dissolved by the reaction mixture by 10.4 times. The duration of incubation did not exceed 60 sec, if 13% homogenate was used. The experiment based on this method showed increased activity of glutathione peroxidase in the brain of mice treated with a derivative of acetaldehyde ammonia during long-term intermittent normobaric hypoxia. These data might reflect activation of glutathione peroxidase.
Introduction. The search for and development of new drugs capable of reducing the severity of neurological deficit in traumatic brain injury are a critical task for investigational pharmacology. Chromone-containing allylmorpholines are a new group of neuroprotective drug candidates that have been shown to inhibit acetylcholinesterase and butyrylcholinesterase, and block N-methyl-D-aspartate receptors in vitro.Aim. This study aimed to evaluate the neuroprotective activity of the allylmorpholine derivative (E)-4-[3-(8-bromo-6-methyl-4-oxo-4H-chromen- 3-yl)-1-cyclohexylallyl]morpholin-4-ium chloride (33b) in vivo using a rat model of traumatic brain injury.Materials and methods. Traumatic brain injury was induced using the controlled cortical impact model. The allylmorpholine derivative was administered intraperitoneally at 1, 10, or 50 mg × kg-1 b.w. at 1 h after trauma induction, and then daily for the next 6 d. The neurological deficit was assessed using the Limb Placing, Open Field, Elevated Plus Maze, Beam Walking, and Cylinder tests.Results and discussion. At all doses administered, the allylmorpholine derivative had no positive effect on the motor function or exploratory behavior following traumatic brain injury. In the Elevated Plus Maze, 10 mg × kg-1 b.w. of the compound further suppressed exploratory behaviour in the injured animals, which appears to be consistent with its sedative properties observed previously in zebrafish.Conclusion. Despite the previously described in vitro affinity of allylmorpholines towards several molecular targets crucial for the pathogenesis of brain trauma and posttraumatic functional recovery, an allylmorpholine derivative had no neuroprotective effect in a rat model of traumatic brain injury in this study. These results further emphasize the importance of in vivo evaluation of potential neuroprotective drug candidates.
Introduction. In modern pharmacology, more and more widely used molecular complexes (MC) based on donor-acceptor or, on weaker, intermolecular interactions, to stabilize dosage forms in the composition of pharmaceutical substances or their targeted delivery. This trend is actively developing, because the molecules forming MK, which has a certain composition and spatial structure, are preserved and can be released unchanged. The use of MC in tandem with "classical" metal-containing coordination compounds, which enhance or modify the action of the active component, allows the development of new, more effective drugs with optimized bioavailability and activity.Aim. Evaluation of the wound-healing effect of new substances based on aqueous systems containing coordination compounds of copper(II) or zinc with MC adenosine-copolymer of N-vinylpyrrolidone, in comparison with the drug Depantol® on a model of thermal burn in mice.Materials and methods. Mononuclear alainate complexes Cu(Ala)2 · H2O and Zn(Ala)2 (Ala – alainate-anion), copolymer of N-vinylpyrrolidone with crotonic acid (PVP-CA) have been synthesized. The composition of the obtained compounds was confirmed by the data of elemental analysis on a CHN (S) analyzer LECO CHNS (O) 932 (Elemental Microanalysis Ltd, Great Britain). IR spectra of the samples were recorded on a IRAffinity-1 (Shimadzu, Japan) instrument (by tabletting a sample with KBr) and a IRTracer-100 (Shimadzu, Japan) instrument equipped with a Specac Quest ATR attachment (Shimadzu Corporation, Japan). Potentiometric titration of the functional groups of the VP copolymer was performed using a PP-20 pH meter (Sartorius AG, Germany). The solutions of the preparations were prepared by dissolving PVP-KK in polyethylene glycol (PEG-400), followed by the addition of an aqueous dispersion of adenosine (Ad) and the corresponding complex of copper(II) or zinc into the preparation. After modeling a thermal burn of the third degree, the overall mortality in the groups and the dynamics of healing of the injured area were assessed. During the experiment, histological studies of areas of damaged tissue after staining of preparations with hematoxylin and eosin were carried out and a generalized scoring assessment of the characteristics of the burn process was carried out, including an assessment of the width and depth of the formed scar tissue, the severity of inflammatory infiltration and the presence of hemosiderosis in the tissues.Results and discussion. The formation of the MC of the copolymer of N-vinylpyrrolidone with crotonic acid with adenosine made it possible to prepare solutions of preparations containing up to 5 % (wght.) Of the latter. In the obtained samples, the molar ratio of PVP-CA : Ad : M(Ala)2 was 100 : 10 : 1 (M = CuII, Zn), the pH level of the obtained preparations was 7.0–7.1. The resulting funds were applied to the damaged area of the skin in a volume of 0.1 ml/day, each individual, daily for 4 weeks. Introductory substances based on MC PVP-CA : Ad : M(Ala)2 showed a moderate wound healing effect in comparison with the drug Depantol®, based on a water-fat emulsion. Substances that do not contain a metal complex and contain Cu(Ala)2 showed better efficiency in the dynamics of healing a burn injury in comparison with other studied substances, which was combined with a low mortality rate of experimental animals in these groups (3 cases and 2 cases out of 9 individuals, respectively). The reference drug – Depantol®, in turn, showed the best result, probably due to the content in its composition, in addition to dexpanthenol, which is characterized by a wound-healing effect, chlorhexidine antiseptic, and a fatty base, which reduces the dehydration of the injured area.Conclusion. Experimental substances based on aqueous solutions of adenosine-polymer MK showed a moderate wound healing effect comparable to the reference drug, which, however, is of sufficient interest for further study of such compositions, or their modified versions with the addition of antimicrobial components on thermal burn models, in order to creation of new, more effective drugs for the healing of wound surfaces.
Enzymes of glutathione peroxidase (GPX) family, together with peroxiredoxins, form thiol peroxidase superfamily, the property of which is the thiol-dependent catalysis of the hydroperoxide reduction. This property determines them as antioxidant protectors. Among human GPXs the eight forms are known, five of which are selenium-dependent (GPX1,2,3,4, and 6). The most number of facts supporting the substantial role of GPX in functioning of endometrium are linked with the GPX3, which is the secretory GPX. The number of candidate progesterone response elements in the promoter of GPX3 gene prevails over the number of candidate estrogen response elements; GPX3 is upregulated gene during postovulatory phase of reproductive cycle and during pregnancy; in the endometrial stroma, the transcription of Gpx3 is stimulated through the transcription factor HIF1α. Using laboratory animals, the spatial and temporal coincidence of Gpx3 activation and blastocyst implantation was observed. It was confirmed that GPX3 decreases hydrogen peroxide concentration in endometrium in pregnant animals and during in vitro decidualization. The vulnerability of reproductive function to physiological stress at the insufficient expression of GPX3 is hypothesized. The GPX3 enzymatic activity in endometrium is poorly investigated. The has been hypothesized that selenium-containing medications are effective in the endometrium receptivity improvement and in the supporting the normal embryo development (especially during the influence of physiological stressors) by the maintenance of the posttranscriptional, selenium-dependent stage of GPX3 biosynthesis in endometrium. Probably, the GPX3 expression can be increased by the steriods with gestagenic activity (through the increase of Gpx3 transcription, analogously to effect of progesterone). In contrast with the «classic» GPX (GPX1) and probably with most of other members of GPX family, GPX3 has a wide thiol specificity. It is proposed to assess the activity of GPX3 using the reduced homocysteine and cysteine as thiol substrates instead of the reduced glutathione.
Изучена нейротропная активность нового соединения аминоэтанола с бутандиовой и транс-этилен-1,2-дикарбоновой кислотами — (2E)-4-[2-(диэтиламино)этокси]-4-оксобут-2-еновой кислоты бутандиоата (2:1) — при курсовом пероральном введении (10 мг/кг) на фоне ишемии головного мозга, вызванной двусторонней перманентной перевязкой общих сонных артерий у крыс. У животных оценивали ориентировочно-исследовательское поведение и координацию движений. По активности производное аминоэтанола сопоставимо с действием цитиколина (500 мг/кг) и цитофлавина (170 мг/кг).
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