Introduction: Every year the importance of the normal functioning of the endothelial layer of the vascular wall in maintaining the health of the body becomes more and more obvious. The physiological role of the endothelium: The endothelium is a metabolically active organ actively involved in the regulation of hemostasis, modulation of inflammation, maintenance of hemovascular homeostasis, regulation of angiogenesis, vascular tone, and permeability. Risk factors for the development of endothelial dysfunction: Currently, insufficient bioavailability of nitric oxide is considered the most significant risk factor for endothelial dysfunction. Mechanisms of development of endothelial dysfunction: The genesis of endothelial dysfunction is a multifactorial process. Among various complex mechanisms, this review examines oxidative stress, inflammation, hyperglycemia, vitamin D deficiency, dyslipidemia, excess visceral fat, hyperhomocysteinemia, hyperuricemia, as well as primary genetic defect of endotheliocytes, as the most common causes in the population underlying the development of endothelial dysfunction. Markers of endothelial dysfunction in various diseases: This article discusses the main biomarkers of endothelial dysfunction currently used, as well as promising biomarkers in the future for laboratory diagnosis of this pathology. Therapeutic strategies: Therapeutic approaches to the endothelium in order to prevent or reduce a degree of damage to the vascular wall are briefly described. Conclusion: Endothelial dysfunction is a typical pathological process involved in the pathogenesis of many diseases. Thus, pharmacological agents with endothelioprotective properties can provide more therapeutic benefits than a drug without such an effect.
Introduction: At present, the problem of pharmacological correction of free radical processess emerges full-blown. The aim of the study is an experimental study of the neuroprotective effect of taurine and 3-hydroxypyridine derivatives. Materials and methods: The study was performed in Wistar rats. The neuroprotective effect of the substances was studied in the intracerebral hemorrhage model. Results and discussion: The administration of the studied substances had a positive effect on the survival of the animals within the first day (50% of rats died in the control group, 30% – in the Mexidol- and Ethoxidol-treated groups, and 20% – in LKhT 3-17-treated group). Within the first day after the surgery, all rats with stroke had severe neurological disorders. However, by the 3rd day, the Ethoxidol- and LKhT 3-17-treated rats had a lower neurological deficit. By Day 14, all groups of animals treated with the test substances had a lower severity of post-stroke disorders than those in the control group, which was evident as a 1.5-time lower McGraw Stroke Index score. LKhT 3-17 substance showed the most pronounced neuroprotective effect. Conclusions: The studied derivatives of taurine and 3-hydroxypyridine have a neuroprotective effect, which is manifested in the lower severity of neurological disorders,a more rapid reduction in the signs of neurodegeneration and accelerated hemorrhage processes.
Introduction: In this review, the analysis of technologies for obtaining biologically active proteins from various sources is carried out, and the comparative analysis of technologies for creating producers of biologically active proteins is presented. Special attention is paid to genetically modified animals as bioreactors for the pharmaceutical industry of a new type. The necessity of improving the technology of development transgenic rabbit producers and creating a platform solution for the production of biological products is substantiated. The advantages of using TrB for the production of recombinant proteins: The main advantages of using TrB are the low cost of obtaining valuable complex therapeutic human proteins in readily accessible fluids, their greater safety relative to proteins isolated directly from human blood, and the greater safety of the activity of the native protein. The advantages of the mammary gland as a system for the expression of recombinant proteins: The mammary gland is the organ of choice for the expression of valuable recombinant proteins because milk is easy to collect in large volumes. Methods for obtaining transgenic animals: The modern understanding of the regulation of gene expression and the discovery of new tools for gene editing can increase the efficiency of creating bioreactors for animals and help to obtain high concentrations of the target protein. The advantages of using rabbits as bioreactors producing recombinant proteins in milk: The rabbit is a relatively small animal with a short duration of gestation, puberty and optimal size, capable of producing up to 5 liters of milk per year per female, receiving up to 300 grams of the target protein.
Citation: Danilenko LM, Skachilova SYa, Nadezhdin SV, Timokhina AS, Shcheblykina OV, Kotelnikova AS (2018) Pharmacological screening of substances with cardioprotective effect in the group of 3-oxypyridine derivatives. Research Results in Pharmacology 4(2): 125-131. https://doi. AbstractIntroduction: The search for new compounds with antihypoxic and cardioprotective effects among 3-oxypyridine derivatives is promising. Research objectives:To study the anti-hypoxic and cardioprotective effects of 3-oxypyridine derivatives. Materials and methods:The search for compounds with an antihypoxic effect was carried out on blood leukocytes of rats in in vitro. To simulate hypoxia, Oil for Tissue Culture (SAGE) was used, 500 µl of which was applied into wells over a growth medium in order to block gas exchange. The cardioprotective effect of 3-oxypyridine derivatives was studied in the model of coronary-occlusive myocardial infarction (30 minutes of ischemia, 90 minutes of reperfusion). The level of troponin I (Tn I) was determined as a biochemical marker of myocardial damage. Results and discussion:In the in vitro experiments, when culting white blood cells, the lead compound in the group of 3-oxypyridine derivatives was identified under code LKhT 21-16, which increases the number of viable cells in the presence of hypoxia, surpassing the reference drugs. When confirming the chemical structure of the lead compound, LHT 21-16, a high sensitivity of the NMR spectroscopy method was revealed.In studying the cardioprotective activity in the model of coronary-occlusive myocardial infarction compound LHT 21-16 exerted a marked cardioprotective effect when reducing the size of the necrotic zone and the level of biochemical marker Tn I. Conclusions:3-oxypiridine derivatives have antihypoxic and cardioprotective effects, which shows in a high number of surviving cells in the presence of hypoxia in the in vitro model, a reduced size of the necrotic zone and a reduced level of Tn I in the coronary-occlusive myocardial infarction.
The correction of free radical oxidation processes is one of the most promising strategies of neuroprotection in acute cerebrovascular disorders.The aim of the study is an experimental study of the neuroprotective effects of 3-hydroxypyridine and erythropoietin derivatives, as well as their combined use.Materials and methods. The study was performed on 109 male Wistar rats. The neuroprotective effect of the substances was studied on a hemorrhagic stroke model. The study drugs were administered to the animals intraperitoneally. Carbamylated darbepoetin was administered three times in advance at the dose of 100 µg/kg within intervals of 3 days, the last injection took place 1 hour before the operation (the total dose was 300 mg/kg). Etoxidol was administered once 1 hour before the surgery at the dose of 50 mg/kg. The survival rate, behavioral features and the state of the animals on the 1st, 3rd, 7th and 14th days were recorded, and the morphological assessment of the brain was carried out.Results. The investigated substances had a positive effect on both the survival rate of the animals during the first day and on the 14th day. The best survival rates on the 14th day were recorded in the group of a combined use of ethoxydol and carbamylated darbepoetin (75%). Thus, in this group of rats, a faster recovery of neurological disorders was already distinguished from the first day on. By the 7th day, more than 50% of the rats receiving the combination of the studied drugs, had had a slight neurological deficit (up to 3 points on the McGrow scale); by the 14th day there had been only minor changes in the neurological status in the rats of this group. A pronounced neuroprotective effect of the combination of 3-hydroxypyridine and erythropoietin derivatives has been confirmed by a histological examination of brain slices – a more rapid decrease in the size of perifocal edema and microcirculation disorders, less damage to neurons and glial elements, and faster processes of resorption and organization of hemorrhage. A macroscopic examination of the brain sections stained with triphenyltetrazolium chloride of the dying rats, showed that perifocal necrosis had been the main cause of high mortality in the control group after the 3rd day.Conclusion. As a result of the experiment, the nephroprotective effect of the studied derivatives of 3-hydroxypyridine and erythropoietin has been proved. Moreover, the combination of these drugs has shown a greater neuroprotective activity than their isolated use. The additive effect of these drugs was due to their action mechanism resulting from the synergism of various structures and components of the cells.
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