Pub Date : 2023-08-08DOI: 10.19163/2307-9266-2023-11-2-127-136
O. Belova, V. A. Kurkin, M. Egorov
Licorice herb (Glycyrrhiza glabra L.) is a promising herbal raw material, which can be comprehensively used to develop drugs with an anti-inflammatory action.The aim of the article was to development a quantitative determination method of total flavonoids in Glycyrrhiza glabra L. herbs.Materials and methods. The subjects of research were 5 samples of licorice herb harvested in summer in various places of growing and cultivation. Pinostrobin was used as a standard sample. The registration of the electronic spectra was carried out with a spectrophotometer (Analytik Jena AG, Germany) by differential spectrophotometry, 96% ethanol was used as a solvent.Results. The methods for quantitative determination of total flavonoids in Glycyrrhiza glabra L. was carried out at an analytical wavelength of 310 nm equivalent to pinocembrin. The optimum parameters for the extraction of total flavonoids from Glycyrrhiza glabra L. were as follows: the extractant – 90% ethanol; the «raw material-extractant» ratio was 1:50; the extraction time was 60 min; the degree of atomization was 2 mm. The content of total flavonoids for the Glyccyrhiza glabra L. herb has been determined, it varies from 0.39±0.002 to 3.41±0.015% with the humidity of the vegetative raw material from 9.97±0.003 to 10.03±0.003% depending on the place of the vegetation, cultivation and year of the raw material collection. The error of the single determination with a 95% confidence level was ±0.73%.Conclusion. The developed methods for the quantitative determination of total flavonoids in Glycyrrhiza glabra L. herbs can be used to solve the issues of standardization of these medicinal plant raw materials.
{"title":"Quantitative determination of total flavonoids in Glycyrrhiza Glabra L. herbs","authors":"O. Belova, V. A. Kurkin, M. Egorov","doi":"10.19163/2307-9266-2023-11-2-127-136","DOIUrl":"https://doi.org/10.19163/2307-9266-2023-11-2-127-136","url":null,"abstract":"Licorice herb (Glycyrrhiza glabra L.) is a promising herbal raw material, which can be comprehensively used to develop drugs with an anti-inflammatory action.The aim of the article was to development a quantitative determination method of total flavonoids in Glycyrrhiza glabra L. herbs.Materials and methods. The subjects of research were 5 samples of licorice herb harvested in summer in various places of growing and cultivation. Pinostrobin was used as a standard sample. The registration of the electronic spectra was carried out with a spectrophotometer (Analytik Jena AG, Germany) by differential spectrophotometry, 96% ethanol was used as a solvent.Results. The methods for quantitative determination of total flavonoids in Glycyrrhiza glabra L. was carried out at an analytical wavelength of 310 nm equivalent to pinocembrin. The optimum parameters for the extraction of total flavonoids from Glycyrrhiza glabra L. were as follows: the extractant – 90% ethanol; the «raw material-extractant» ratio was 1:50; the extraction time was 60 min; the degree of atomization was 2 mm. The content of total flavonoids for the Glyccyrhiza glabra L. herb has been determined, it varies from 0.39±0.002 to 3.41±0.015% with the humidity of the vegetative raw material from 9.97±0.003 to 10.03±0.003% depending on the place of the vegetation, cultivation and year of the raw material collection. The error of the single determination with a 95% confidence level was ±0.73%.Conclusion. The developed methods for the quantitative determination of total flavonoids in Glycyrrhiza glabra L. herbs can be used to solve the issues of standardization of these medicinal plant raw materials.","PeriodicalId":20031,"journal":{"name":"Pharmacology & Pharmacy","volume":"32 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74662203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-08DOI: 10.19163/2307-9266-2023-11-2-161-172
A. Alekhin, T. N. Erivantseva, V. Ryazhenov, N. N. Lyskov, N. Alekhina, M. M. Kuznetsova
The aim of the work was to study the legal aspects of the legislative regulation for manufacturing medicines in a pharmacy organization.Materials and methods. Databases of ConsultantPlus, Cyberleninka, Food and Drug Administration (FDA), European Medicines Agency (EMA), National Center for Biotechnology Information (NCBI), PubMed, e-library, WIPO Lex were used as search sources. The search was based on the following keywords and phrases: intellectual property, pharmacies+invention, patent, drugs, extemporal+production, orphan+diseases, as well as their Russian counterparts. 133 sources of information, including scientific articles and regulations, were found out; 50 have been included in this review. The analysis of information sources published from 2013 to 2023, was determined by the peculiarities of legislation changes in this area.Results. The article provided an overview of modern, including regulatory practice, pharmaceutical manufacturing in the Russian Federation, and also analyzed the benefits of this activity for the medical community, patients and the state. At the same time, the individualization of drug treatment has made it possible to work out systemic solutions for developing drug therapy methods for special groups of patients for whom the economic feasibility of a pharmaceutical registration and launching such drugs onto the market has been brought into challenge. In addition, pharmacy manufacturing is an accessible tool in the study of the drugs prescribed by a doctor not in accordance with the instructions for medical use (off-label) or in the dosage forms/dosages that are not on the market. Extemporaneous manufacturing can be also a part of the process of “repositioning” drugs on the market, subject to compliance with the requirements for pharmacy manufacturing and control of the prescribed drugs safety. The possibility of pharmaceutic drug manufacturing also makes it possible to partially resolve issues related to intellectual property. As a result of the carried out analysis, the following hypothesis was confirmed: the legislative changes have a similar legal assessment both in Russia and abroad and correspond to the legal practice in resolving intellectual property issues in relation to pharmacy organizations.Conclusion. The renewal of a pharmacy production will improve the availability of the drug care to the population, taking into account individual dosages and dosage forms in various therapeutic areas, and can also become a tool for repositioning drugs or clinical testing of new molecules for rare incurable diseases.
{"title":"New role of extemporaneous manufacturing in regulating drug products access onto the market","authors":"A. Alekhin, T. N. Erivantseva, V. Ryazhenov, N. N. Lyskov, N. Alekhina, M. M. Kuznetsova","doi":"10.19163/2307-9266-2023-11-2-161-172","DOIUrl":"https://doi.org/10.19163/2307-9266-2023-11-2-161-172","url":null,"abstract":"The aim of the work was to study the legal aspects of the legislative regulation for manufacturing medicines in a pharmacy organization.Materials and methods. Databases of ConsultantPlus, Cyberleninka, Food and Drug Administration (FDA), European Medicines Agency (EMA), National Center for Biotechnology Information (NCBI), PubMed, e-library, WIPO Lex were used as search sources. The search was based on the following keywords and phrases: intellectual property, pharmacies+invention, patent, drugs, extemporal+production, orphan+diseases, as well as their Russian counterparts. 133 sources of information, including scientific articles and regulations, were found out; 50 have been included in this review. The analysis of information sources published from 2013 to 2023, was determined by the peculiarities of legislation changes in this area.Results. The article provided an overview of modern, including regulatory practice, pharmaceutical manufacturing in the Russian Federation, and also analyzed the benefits of this activity for the medical community, patients and the state. At the same time, the individualization of drug treatment has made it possible to work out systemic solutions for developing drug therapy methods for special groups of patients for whom the economic feasibility of a pharmaceutical registration and launching such drugs onto the market has been brought into challenge. In addition, pharmacy manufacturing is an accessible tool in the study of the drugs prescribed by a doctor not in accordance with the instructions for medical use (off-label) or in the dosage forms/dosages that are not on the market. Extemporaneous manufacturing can be also a part of the process of “repositioning” drugs on the market, subject to compliance with the requirements for pharmacy manufacturing and control of the prescribed drugs safety. The possibility of pharmaceutic drug manufacturing also makes it possible to partially resolve issues related to intellectual property. As a result of the carried out analysis, the following hypothesis was confirmed: the legislative changes have a similar legal assessment both in Russia and abroad and correspond to the legal practice in resolving intellectual property issues in relation to pharmacy organizations.Conclusion. The renewal of a pharmacy production will improve the availability of the drug care to the population, taking into account individual dosages and dosage forms in various therapeutic areas, and can also become a tool for repositioning drugs or clinical testing of new molecules for rare incurable diseases.","PeriodicalId":20031,"journal":{"name":"Pharmacology & Pharmacy","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85690174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-08DOI: 10.19163/2307-9266-2023-11-2-149-160
S. Russkikh, E. Tarasenko, L. Moskvicheva, S. A. Orlov, A. Tryakin, A. V. Vorobeva, O. A. Beneslavskaya, V. I. Makarova, E. Putilina, S. A. Utkin
The aim of the work was to analyze Russian and foreign experience in the regulation and application practice of “off-label” drugs in order to develop recommendations on the optimization of their application in clinical practice.Material and methods. The analysis of scientific articles and legal documents of the Russian Federation and foreign countries published from 2011 to 2022 on the websites Consultant Plus, FDA, EMA, NCBI, e-library, as well as a qualitative sociological study conducted in May-August 2022 ‒ 11 in-depth interviews with experts in the field of the healthcare system of the Russian Federation.Results. The social and economic aspects have been considered and the list of legal problems in the application practice of “off-label” drugs has been disclosed. A state analysis of the regulatory and legal framework on the drugs application practice by healthcare professionals in the absence of registered indications for “off-label” drugs use has been presented. The use of an unregistered medicinal product in the territory of the Russian Federation in everyday medical practice has been considered. The analysis of the Russian and foreign experience in regulating the use of drugs in the absence of their registration in the country, as well as the absence of registration of some indications for their prescription in the instructions for the medical use of such drugs has been also carried out. The authors have formulated the key problems of the use of “off-label” drugs in clinical practice. Based on the results of the in-depth interviews, the recommendations of the expert community on the ways to optimize the use of “off-label” drugs have been identified and concretized.Conclusion. The results of this study made it possible to formulate recommendations for expanding the ability of specialists to prescribe “off-label” drugs treatment while maintaining a proper degree of the state control over this process: a legislative consolidation of the regional health authorities’ obligations and responsibilities on the drug provision; creating an open and transparent system for the “off-label” drugs use by patients and their legal representatives, the mandatory full information of the patient about the fact of using the “off-label” drug, as well as the risk and nature of the development of possible adverse reactions. When prescribing these drugs, the patient safety should be the top priority.
{"title":"“Off-label” drugs: legal problems and socio-economic aspects of application practice","authors":"S. Russkikh, E. Tarasenko, L. Moskvicheva, S. A. Orlov, A. Tryakin, A. V. Vorobeva, O. A. Beneslavskaya, V. I. Makarova, E. Putilina, S. A. Utkin","doi":"10.19163/2307-9266-2023-11-2-149-160","DOIUrl":"https://doi.org/10.19163/2307-9266-2023-11-2-149-160","url":null,"abstract":"The aim of the work was to analyze Russian and foreign experience in the regulation and application practice of “off-label” drugs in order to develop recommendations on the optimization of their application in clinical practice.Material and methods. The analysis of scientific articles and legal documents of the Russian Federation and foreign countries published from 2011 to 2022 on the websites Consultant Plus, FDA, EMA, NCBI, e-library, as well as a qualitative sociological study conducted in May-August 2022 ‒ 11 in-depth interviews with experts in the field of the healthcare system of the Russian Federation.Results. The social and economic aspects have been considered and the list of legal problems in the application practice of “off-label” drugs has been disclosed. A state analysis of the regulatory and legal framework on the drugs application practice by healthcare professionals in the absence of registered indications for “off-label” drugs use has been presented. The use of an unregistered medicinal product in the territory of the Russian Federation in everyday medical practice has been considered. The analysis of the Russian and foreign experience in regulating the use of drugs in the absence of their registration in the country, as well as the absence of registration of some indications for their prescription in the instructions for the medical use of such drugs has been also carried out. The authors have formulated the key problems of the use of “off-label” drugs in clinical practice. Based on the results of the in-depth interviews, the recommendations of the expert community on the ways to optimize the use of “off-label” drugs have been identified and concretized.Conclusion. The results of this study made it possible to formulate recommendations for expanding the ability of specialists to prescribe “off-label” drugs treatment while maintaining a proper degree of the state control over this process: a legislative consolidation of the regional health authorities’ obligations and responsibilities on the drug provision; creating an open and transparent system for the “off-label” drugs use by patients and their legal representatives, the mandatory full information of the patient about the fact of using the “off-label” drug, as well as the risk and nature of the development of possible adverse reactions. When prescribing these drugs, the patient safety should be the top priority.","PeriodicalId":20031,"journal":{"name":"Pharmacology & Pharmacy","volume":"58 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86701626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-08DOI: 10.19163/2307-9266-2023-11-2-137-148
O. Radaeva, L. Balykova, K. Zaslavskaya, Y. Kostina, N. Pyataev, N. Selezneva, A. Klimova, I. Chegodaeva, K. N. Koryanova, A. V. Taganov, P. A. Bely
The aim of the work was to study сytokine response characteristics in the group of persons contacted by a novel coronavirus infection depending on the development of the disease over the next 14 days. Herewith, for the immunocorrection with a preparation based on RNA double-stranded sodium salt (RADAMIN®VIRO) causing a secondary reduction in the risk of COVID-19 in the analyzed group, potential targets had been selected.Materials and methods. A double-blind, placebo-controlled study of the drug based on RNA double-stranded sodium salt therapeutic effects was conducted in a group of patients who had been in contact with the persons having a confirmed diagnosis of COVID-19. The method of enzyme immunoassay in dynamics was used to determine the content of interferons alpha and beta (IFNα and IFNβ, respectively), interleukin-1β and -10 (IL1β and IL-10, respectively) in the blood serum and saliva in the contact persons, with a retrospective assessment of changes depending on the administration of the drug or placebo, as well as the development of COVID-19.Results. In the course of the presented study, it was demonstrated that the established content of IFNα (less than 28 pg/ml) and IFNβ (less than 12 pg/ml) in saliva on the 1st–2nd contact days is a predictor of an increased risk of developing COVID-19. Herewith, the increase degree in these immunoregulatory peptides in the interval of 2–3 contact days is important: IFNα and IFNβ allows leveling the negative prognosis in patients by 250% or more. The lowest rates (p <0.001) of INFα on the 1st–2nd contact days, as well as an increase of less than 21% by the 3rd day, were observed in persons with a waist circumference of more than 80/94 cm (women/men). The incidence in this group was higher and amounted to 85% (16 out of 20 people). The predictor role of IL-1β and IL-10 in the blood and saliva in relation to the start of the infectious process was not revealed. The administration of drug based on RNA double-stranded sodium salt to the contact patients made it possible to correct the interferon response in the form of an increase in the content of IFNα and IFNβ, as well as to reduce the incidence in comparison with the placebo group.Conclusion. Differences in the interferon regulation upon contact with SARS-CoV-2 in the form of lower INF α and β levels, as well as a slightly pronounced growth dynamics in the interval of the first 3 days, influenced the increased risk of developing COVID-19. RADAMIN®VIRO can be recommended as a means of post-exposure prophylaxis of COVID-19 for both medical institutions and for caregivers and / or contacts with COVID-19 patients.
{"title":"Analysis of cytokine response characteristics and immunopathogenetic effects of double-stranded sodium salt RNA-based drug for postexposure prophylaxis against novel coronavirus infection: double-blind, placebo-controlled trial","authors":"O. Radaeva, L. Balykova, K. Zaslavskaya, Y. Kostina, N. Pyataev, N. Selezneva, A. Klimova, I. Chegodaeva, K. N. Koryanova, A. V. Taganov, P. A. Bely","doi":"10.19163/2307-9266-2023-11-2-137-148","DOIUrl":"https://doi.org/10.19163/2307-9266-2023-11-2-137-148","url":null,"abstract":"The aim of the work was to study сytokine response characteristics in the group of persons contacted by a novel coronavirus infection depending on the development of the disease over the next 14 days. Herewith, for the immunocorrection with a preparation based on RNA double-stranded sodium salt (RADAMIN®VIRO) causing a secondary reduction in the risk of COVID-19 in the analyzed group, potential targets had been selected.Materials and methods. A double-blind, placebo-controlled study of the drug based on RNA double-stranded sodium salt therapeutic effects was conducted in a group of patients who had been in contact with the persons having a confirmed diagnosis of COVID-19. The method of enzyme immunoassay in dynamics was used to determine the content of interferons alpha and beta (IFNα and IFNβ, respectively), interleukin-1β and -10 (IL1β and IL-10, respectively) in the blood serum and saliva in the contact persons, with a retrospective assessment of changes depending on the administration of the drug or placebo, as well as the development of COVID-19.Results. In the course of the presented study, it was demonstrated that the established content of IFNα (less than 28 pg/ml) and IFNβ (less than 12 pg/ml) in saliva on the 1st–2nd contact days is a predictor of an increased risk of developing COVID-19. Herewith, the increase degree in these immunoregulatory peptides in the interval of 2–3 contact days is important: IFNα and IFNβ allows leveling the negative prognosis in patients by 250% or more. The lowest rates (p <0.001) of INFα on the 1st–2nd contact days, as well as an increase of less than 21% by the 3rd day, were observed in persons with a waist circumference of more than 80/94 cm (women/men). The incidence in this group was higher and amounted to 85% (16 out of 20 people). The predictor role of IL-1β and IL-10 in the blood and saliva in relation to the start of the infectious process was not revealed. The administration of drug based on RNA double-stranded sodium salt to the contact patients made it possible to correct the interferon response in the form of an increase in the content of IFNα and IFNβ, as well as to reduce the incidence in comparison with the placebo group.Conclusion. Differences in the interferon regulation upon contact with SARS-CoV-2 in the form of lower INF α and β levels, as well as a slightly pronounced growth dynamics in the interval of the first 3 days, influenced the increased risk of developing COVID-19. RADAMIN®VIRO can be recommended as a means of post-exposure prophylaxis of COVID-19 for both medical institutions and for caregivers and / or contacts with COVID-19 patients.","PeriodicalId":20031,"journal":{"name":"Pharmacology & Pharmacy","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87977174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-07DOI: 10.19163/2307-9266-2023-11-2-114-126
E. V. Lakomkina, G. Atazhanova, S. Akhmetova, I. N. Zilfikarov
The article reflects the results of the essential oils selection for the compositions with antibacterial and antifungal properties. The technology of their production is represented.The aim of the work was the development of technology and the study structure of new essential oils compositions with antibacterial and antifungal activities.Material and methods. The following plants have been used in the work: the herb of Hyssopus ambiguus (Trautv.) Iljin, the herb of Thymus crebrifolius Klokov, the herb of Thymus marschallianus Willd, the herb of Thymus serpyllum L., and the essential oils obtained from them. The composition of the essential oils was determined by Gas Chromatography Mass Spectrometry. The main physical and chemical parameters of the compositions were evaluated in accordance with the requirements of the Russian State Pharmacopoeia, the XIVth edition. The tests for the antimicrobial activity were carried out using the strains of Staphylococcus aureus ATCC 6538, Bacillus subtilis ATCC 6633, Escherichia coli ATCC 25922, Candida albicans ATCC 10231.Results. Compositions with an activity against microorganisms Staphylococcus aureus, Bacillus subtilis, Escherichia coli and fungi Candida albicans have been obtained and studied. The composition based on essential oils of Hyssopus ambiguus (Trautv.) Iljin and Thymus marschallianus Willd. contained 139 components, the main ones of which are eucalyptol (6.51%) and terpinen-4-ol (1.95%). The composition of essential oils of Hyssopus ambiguus (Trautv. Iljin) and Thymus crebrifolius Klokov contained 137 components (eucalyptol (20.37%), terpinen-4-ol (7.03%), Ʈ-muurol (2.28%), γ-terpinene (2.23%), β-myrcene (2.09%), etc.). The composition of the essential oils of Hyssopus ambiguus (Trautv.) Iljin and Thymus serpyllum L. contained 149 components (the main ones are eucalyptol (7.33%) and α-terpineol (0.9%)).Conclusion. The technology has been proposed and the structure of the essential oils compositions with antibacterial and antifungal activities has been established.
{"title":"Development of composition and technology for obtaining antimicrobial composition based on mono- and sesquiterpenoids","authors":"E. V. Lakomkina, G. Atazhanova, S. Akhmetova, I. N. Zilfikarov","doi":"10.19163/2307-9266-2023-11-2-114-126","DOIUrl":"https://doi.org/10.19163/2307-9266-2023-11-2-114-126","url":null,"abstract":"The article reflects the results of the essential oils selection for the compositions with antibacterial and antifungal properties. The technology of their production is represented.The aim of the work was the development of technology and the study structure of new essential oils compositions with antibacterial and antifungal activities.Material and methods. The following plants have been used in the work: the herb of Hyssopus ambiguus (Trautv.) Iljin, the herb of Thymus crebrifolius Klokov, the herb of Thymus marschallianus Willd, the herb of Thymus serpyllum L., and the essential oils obtained from them. The composition of the essential oils was determined by Gas Chromatography Mass Spectrometry. The main physical and chemical parameters of the compositions were evaluated in accordance with the requirements of the Russian State Pharmacopoeia, the XIVth edition. The tests for the antimicrobial activity were carried out using the strains of Staphylococcus aureus ATCC 6538, Bacillus subtilis ATCC 6633, Escherichia coli ATCC 25922, Candida albicans ATCC 10231.Results. Compositions with an activity against microorganisms Staphylococcus aureus, Bacillus subtilis, Escherichia coli and fungi Candida albicans have been obtained and studied. The composition based on essential oils of Hyssopus ambiguus (Trautv.) Iljin and Thymus marschallianus Willd. contained 139 components, the main ones of which are eucalyptol (6.51%) and terpinen-4-ol (1.95%). The composition of essential oils of Hyssopus ambiguus (Trautv. Iljin) and Thymus crebrifolius Klokov contained 137 components (eucalyptol (20.37%), terpinen-4-ol (7.03%), Ʈ-muurol (2.28%), γ-terpinene (2.23%), β-myrcene (2.09%), etc.). The composition of the essential oils of Hyssopus ambiguus (Trautv.) Iljin and Thymus serpyllum L. contained 149 components (the main ones are eucalyptol (7.33%) and α-terpineol (0.9%)).Conclusion. The technology has been proposed and the structure of the essential oils compositions with antibacterial and antifungal activities has been established.","PeriodicalId":20031,"journal":{"name":"Pharmacology & Pharmacy","volume":"77 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76928365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-08-07DOI: 10.19163/2307-9266-2023-11-2-104-113
D. Kurkin, D. A. Bakulin, E. Morkovin, Y. Gorbunova, A. Strygin, T. M. Andriashvili, A. Sokolova, N. S. Bolokhov, V. E. Pustynnikov, E. A. Fomichev, A. V. Baskova, S. S. Polodyants, A. V. Kasparova
The aim of the study was to evaluate a cerebroprotective activity of the sitagliptin and aminoguanidine combination in rats with an acute and chronic cerebral circulation insufficiency, as well as with a traumatic brain injury.Materials and methods. The study was carried out on male Wistar rats in 3 stages using, respectively, a model of a chronic pathology: a chronic cerebral circulation insufficiency (CCCI), as well as 2 models of the acute brain injury (BI): an acute cerebral circulation insufficiency (ACCI), and a traumatic brain injury (TBI). А CCCI was modeled by a bilateral stenosis of the common carotid arteries (by 50%), a model of a hemorrhagic stroke caused by an intracerebral injection of the autologous blood was used as a stroke, a TBI was modeled by a mechanical damage to the brain tissue. To assess the pathology course severity, the following tests were used: Adhesion test, Open field, Morris water maze test, as well as Garcia and Combs&D’Alecy scales. In the animals with an acute damage to the brain at the end of the experiment, the severity of edema of the affected hemisphere was also determined. The treatment was with sitagliptin (10 mg/kg), aminoguanidine (25 mg/kg), or a combination thereof. The obtained data were subjected to the statistical processing.Results. In the course of the study, it was found out that the administration of a sitagliptin and aminoguanidine combination, unlike each of the components, had a cerebroprotective effect in the animals with a chronic or acute damage to the brain, reducing the severity of psychoneurological (cognitive and sensory-motor) disorders, as well as the brain edema.Conclusion. Aminoguanidine, as an iNOS blocker, enhances the action of sitagliptin, preventing the brain edema development and reducing the neurological deficit severity (the severity of cognitive and sensory-motor impairments) in the animals with an acute and chronic cerebral circulation insufficiency.
{"title":"Cerebroprotective effect of sitagliptin and aminoguanidine combination in disorders of cerebral circulation","authors":"D. Kurkin, D. A. Bakulin, E. Morkovin, Y. Gorbunova, A. Strygin, T. M. Andriashvili, A. Sokolova, N. S. Bolokhov, V. E. Pustynnikov, E. A. Fomichev, A. V. Baskova, S. S. Polodyants, A. V. Kasparova","doi":"10.19163/2307-9266-2023-11-2-104-113","DOIUrl":"https://doi.org/10.19163/2307-9266-2023-11-2-104-113","url":null,"abstract":"The aim of the study was to evaluate a cerebroprotective activity of the sitagliptin and aminoguanidine combination in rats with an acute and chronic cerebral circulation insufficiency, as well as with a traumatic brain injury.Materials and methods. The study was carried out on male Wistar rats in 3 stages using, respectively, a model of a chronic pathology: a chronic cerebral circulation insufficiency (CCCI), as well as 2 models of the acute brain injury (BI): an acute cerebral circulation insufficiency (ACCI), and a traumatic brain injury (TBI). А CCCI was modeled by a bilateral stenosis of the common carotid arteries (by 50%), a model of a hemorrhagic stroke caused by an intracerebral injection of the autologous blood was used as a stroke, a TBI was modeled by a mechanical damage to the brain tissue. To assess the pathology course severity, the following tests were used: Adhesion test, Open field, Morris water maze test, as well as Garcia and Combs&D’Alecy scales. In the animals with an acute damage to the brain at the end of the experiment, the severity of edema of the affected hemisphere was also determined. The treatment was with sitagliptin (10 mg/kg), aminoguanidine (25 mg/kg), or a combination thereof. The obtained data were subjected to the statistical processing.Results. In the course of the study, it was found out that the administration of a sitagliptin and aminoguanidine combination, unlike each of the components, had a cerebroprotective effect in the animals with a chronic or acute damage to the brain, reducing the severity of psychoneurological (cognitive and sensory-motor) disorders, as well as the brain edema.Conclusion. Aminoguanidine, as an iNOS blocker, enhances the action of sitagliptin, preventing the brain edema development and reducing the neurological deficit severity (the severity of cognitive and sensory-motor impairments) in the animals with an acute and chronic cerebral circulation insufficiency.","PeriodicalId":20031,"journal":{"name":"Pharmacology & Pharmacy","volume":"94 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80619528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-30DOI: 10.19163/2307-9266-2023-11-1-89-100
I. Kodonidi, A. V. Bicherov, E. Manvelyan, A. Kolodina, A. A. Bicherov, M. Manvelyan, A. Ivchenko, N. Vdovenko-Martynova, A. T. Navalieva, M. Manvelyan
Quinazolin-4(3Н)-one derivatives are characterized by a wide range of pharmacological properties, among which the most significant one is a pronounced effect on the central nervous system. In this regard, a molecular design of biologically active compounds that have an analgesic activity due to the formation of ligand-receptor complexes with nociceptive and dopamine receptors, has been performed.The aim of the study was a molecular design and a subsequent targeted synthesis of 2-phenyl- and 2-benzyl derivatives of 4(3H)-quinazolinone with an analgesic activity, as well as the creation of a mathematical model in order to identify significant molecular descriptors.Materials and methods. A molecular design was carried out by a logical-structural approach using the PASS program with the identification of the biological activity of the predicted structures, as well as the energy calculation of the ligand-receptor interaction. The synthesis of 2-phenyl derivatives of 4(3H)-quinazolinone was carried out by the reaction of 2-aminobenzamide with aromatic aldehydes in polyphosphoric acid when heated, while the 2-benzyl derivatives were synthesized by fusing amides of anthranilic and homoveratric acids followed by sulfonation with sulfuric acid. The analgesic activity of the synthesized compounds was studied in the models of nociceptive reactions induced by chemical stimuli (a formalin test and “acetic acid writhings”).Results. A molecular design made it possible to identify promising structures in the series of 4(3H)-quinazolinone derivatives that affect nociceptive and dopamine receptors and have an analgesic activity. A modification was made to the synthesis of 2-phenyl- and 2-benzyl derivatives of 4(3H)-quinazolinone in order to increase the yield of the target products by a simpler and more cost-effective method. The predicted compounds were synthesized by cyclocondensation of anthranilic acid amide with aromatic aldehydes or with homoveraic acid amide. It follows from the primary pharmacological studies results that the synthesized substances are promising from the point of view of creating painkillers based on them. A structure-activity relationship between the molecular descriptors, which are largely responsible for the analgesic activity, and the results of biological tests, has been revealed.Conclusion. The use of computer modelling made it possible to identify the amino acid residues involved in the formation of the ligand-receptor complex with the nociceptive receptor, and to construct a mathematical model to explain the analgesic activity of 2-phenyl- and 2-benzyl derivatives of 4(3H)-quinazolinone. Modified procedures for the synthesis of target compounds have been proposed. The obtained coefficients of the approximation between the theoretical values and the data of the pharmacological experiment make it possible to state a sufficient reliability of the carried out studies.
{"title":"Synthesis of 2-phenyl- and 2-benzyl derivatives of 4(3Н)-quinazolinone with analgesic activity","authors":"I. Kodonidi, A. V. Bicherov, E. Manvelyan, A. Kolodina, A. A. Bicherov, M. Manvelyan, A. Ivchenko, N. Vdovenko-Martynova, A. T. Navalieva, M. Manvelyan","doi":"10.19163/2307-9266-2023-11-1-89-100","DOIUrl":"https://doi.org/10.19163/2307-9266-2023-11-1-89-100","url":null,"abstract":"Quinazolin-4(3Н)-one derivatives are characterized by a wide range of pharmacological properties, among which the most significant one is a pronounced effect on the central nervous system. In this regard, a molecular design of biologically active compounds that have an analgesic activity due to the formation of ligand-receptor complexes with nociceptive and dopamine receptors, has been performed.The aim of the study was a molecular design and a subsequent targeted synthesis of 2-phenyl- and 2-benzyl derivatives of 4(3H)-quinazolinone with an analgesic activity, as well as the creation of a mathematical model in order to identify significant molecular descriptors.Materials and methods. A molecular design was carried out by a logical-structural approach using the PASS program with the identification of the biological activity of the predicted structures, as well as the energy calculation of the ligand-receptor interaction. The synthesis of 2-phenyl derivatives of 4(3H)-quinazolinone was carried out by the reaction of 2-aminobenzamide with aromatic aldehydes in polyphosphoric acid when heated, while the 2-benzyl derivatives were synthesized by fusing amides of anthranilic and homoveratric acids followed by sulfonation with sulfuric acid. The analgesic activity of the synthesized compounds was studied in the models of nociceptive reactions induced by chemical stimuli (a formalin test and “acetic acid writhings”).Results. A molecular design made it possible to identify promising structures in the series of 4(3H)-quinazolinone derivatives that affect nociceptive and dopamine receptors and have an analgesic activity. A modification was made to the synthesis of 2-phenyl- and 2-benzyl derivatives of 4(3H)-quinazolinone in order to increase the yield of the target products by a simpler and more cost-effective method. The predicted compounds were synthesized by cyclocondensation of anthranilic acid amide with aromatic aldehydes or with homoveraic acid amide. It follows from the primary pharmacological studies results that the synthesized substances are promising from the point of view of creating painkillers based on them. A structure-activity relationship between the molecular descriptors, which are largely responsible for the analgesic activity, and the results of biological tests, has been revealed.Conclusion. The use of computer modelling made it possible to identify the amino acid residues involved in the formation of the ligand-receptor complex with the nociceptive receptor, and to construct a mathematical model to explain the analgesic activity of 2-phenyl- and 2-benzyl derivatives of 4(3H)-quinazolinone. Modified procedures for the synthesis of target compounds have been proposed. The obtained coefficients of the approximation between the theoretical values and the data of the pharmacological experiment make it possible to state a sufficient reliability of the carried out studies.","PeriodicalId":20031,"journal":{"name":"Pharmacology & Pharmacy","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91246611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-30DOI: 10.19163/2307-9266-2023-11-1-72-88
L. Balykova, O. Radaeva, K. Zaslavskaya, A. V. Taganov, P. A. Bely, K. Zakharov, V. Popova, T. Chudinovskikh, S. V. Teplykh, I. V. Balaban, R. S. Kozlov, N. V. Kirichenko, E. Simakina, K. N. Koryanova, D. Pushkar
The aim of the study was to evaluate the efficacy and safety of an RNA double-stranded sodium salt drug, a lyophilisate for a solution preparation for an intramuscular and subcutaneous administration, as a means of post-exposure COVID-19 prophylaxis in comparison with placebo.Material and methods. A double-blind, placebo-controlled, multicenter, randomized phase III clinical trial was conducted to evaluate the efficacy and safety of a double-stranded sodium salt RNA drug (RADAMIN®VIRO), a lyophilisate for preparing a solution for intramuscular and subcutaneous administration as a means of post-exposure prophylaxis of COVID-19. The study was conducted in 10 research centers in the Russian Federation from May 31, 2022 to January 17, 2023. The study included men and women aged ≥18 years who cohabitate with a person with a documented COVID-19 diagnosis and do not have symptoms characteristic of COVID-19. At the randomization stage, the subjects were assigned to one of two groups: group 1 (n=400) received a study drug RADAMIN®VIRO 5 mg (1 vial) intramuscularly once a day; group 2 (n=400) received placebo 1 vial intramuscularly once a day. The total duration of the study for each subject was no more than 30 days.Results. By day 10-11, in the double-stranded sodium salt RNA preparation group, the proportion of the subjects with confirmed COVID-19 and at least 1 symptom characteristic of COVID-19 was 5.76% (23/399), and in the placebo group – 11. 03% (44/399). The difference in proportions between the study drug and placebo groups was 0.0526 (5.26%), the 95% confidence interval (CI) for the difference in proportions between the groups was -95% CI [0.0123;0.0937]). More than 94% of single-dose subjects did not become infected with COVID-19 with any symptoms during the 11 days of the follow-up. As a result of a comparative analysis, it was shown that the infection frequency in the study drug group was statistically significantly (almost twice) less than in the comparison group, which indicates a high efficiency and expediency of using the double-stranded sodium salt RNA preparation as a means of the post-exposure COVID-19 prophylaxis.Conclusion. Thus, regardless of the vaccination availability, the effectiveness and feasibility of using the study double-stranded sodium salt RNA preparation as a means of the post-exposure COVID-19 prophylaxis was demonstrated not only in medical institutions (outpatient clinics and hospitals), but also in caregivers and/or the persons in contact with COVID-19 patients. The situation was the same in the organizations and enterprises in case of evolution of a mass infection threat and the availability of appropriate medical personnels.
{"title":"Post-exposure prophylaxis of COVID-19: results of double-blind, placebo-controlled, multicenter clinical study evaluation of efficacy and safety of double-stranded sodium salt RNA drug","authors":"L. Balykova, O. Radaeva, K. Zaslavskaya, A. V. Taganov, P. A. Bely, K. Zakharov, V. Popova, T. Chudinovskikh, S. V. Teplykh, I. V. Balaban, R. S. Kozlov, N. V. Kirichenko, E. Simakina, K. N. Koryanova, D. Pushkar","doi":"10.19163/2307-9266-2023-11-1-72-88","DOIUrl":"https://doi.org/10.19163/2307-9266-2023-11-1-72-88","url":null,"abstract":"The aim of the study was to evaluate the efficacy and safety of an RNA double-stranded sodium salt drug, a lyophilisate for a solution preparation for an intramuscular and subcutaneous administration, as a means of post-exposure COVID-19 prophylaxis in comparison with placebo.Material and methods. A double-blind, placebo-controlled, multicenter, randomized phase III clinical trial was conducted to evaluate the efficacy and safety of a double-stranded sodium salt RNA drug (RADAMIN®VIRO), a lyophilisate for preparing a solution for intramuscular and subcutaneous administration as a means of post-exposure prophylaxis of COVID-19. The study was conducted in 10 research centers in the Russian Federation from May 31, 2022 to January 17, 2023. The study included men and women aged ≥18 years who cohabitate with a person with a documented COVID-19 diagnosis and do not have symptoms characteristic of COVID-19. At the randomization stage, the subjects were assigned to one of two groups: group 1 (n=400) received a study drug RADAMIN®VIRO 5 mg (1 vial) intramuscularly once a day; group 2 (n=400) received placebo 1 vial intramuscularly once a day. The total duration of the study for each subject was no more than 30 days.Results. By day 10-11, in the double-stranded sodium salt RNA preparation group, the proportion of the subjects with confirmed COVID-19 and at least 1 symptom characteristic of COVID-19 was 5.76% (23/399), and in the placebo group – 11. 03% (44/399). The difference in proportions between the study drug and placebo groups was 0.0526 (5.26%), the 95% confidence interval (CI) for the difference in proportions between the groups was -95% CI [0.0123;0.0937]). More than 94% of single-dose subjects did not become infected with COVID-19 with any symptoms during the 11 days of the follow-up. As a result of a comparative analysis, it was shown that the infection frequency in the study drug group was statistically significantly (almost twice) less than in the comparison group, which indicates a high efficiency and expediency of using the double-stranded sodium salt RNA preparation as a means of the post-exposure COVID-19 prophylaxis.Conclusion. Thus, regardless of the vaccination availability, the effectiveness and feasibility of using the study double-stranded sodium salt RNA preparation as a means of the post-exposure COVID-19 prophylaxis was demonstrated not only in medical institutions (outpatient clinics and hospitals), but also in caregivers and/or the persons in contact with COVID-19 patients. The situation was the same in the organizations and enterprises in case of evolution of a mass infection threat and the availability of appropriate medical personnels.","PeriodicalId":20031,"journal":{"name":"Pharmacology & Pharmacy","volume":"36 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84839925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-28DOI: 10.19163/2307-9266-2023-11-1-4-18
K. Kalitin, A. Spasov, O. Mukha
The development of new drugs to combat neuroinflammation is highly relevant as it opens up possibilities for the treatment of a wide range of diseases, including Alzheimer’s disease, Parkinson’s disease, epilepsy, schizophrenia, depression, and others. Kappa-opioid agonists represent a promising class of compounds with а high potential to be used in the treatment of neurological conditions accompanied by neuroinflammation.The aim of the study was to provide a summary of the current strategies employed to evaluate the neurotropic anti-inflammatory effects of kappa-opioid ligands in laboratory animals with induced neuroinflammation.Materials and methods. The databases, such as Google Scholar, PubMed, ScienceDirect, Scopus, e-Library were used as search tools. The search comprised the following keywords and phrases in Russian and English: kappa opioids + neuroinflammation; kappa opioid receptors + neuroinflammation; neuroinflammation models; neuroinflammation models in rats, neuroinflammation models in mice. 148 relevant articles were found, 122 were included in this review.Results. Various experimental models of neuroinflammation, including chemically-induced and bacterial endotoxin-induced neuroinflammation, as well as traumatic and genetic models in mice and rats were evaluated. In addition, the strengths and limitations of each model were critically assessed to identify the most appropriate and reliable approach for investigating the relationship between neuroinflammation and signaling pathways associated with kappa-opioid receptors.Conclusion. The neurotropic anti-inflammatory activity of kappa-opioid ligands have been comprehensively described. The review discusses both experimental models where the effects of kappa-opioid agonists have been investigated, as well as the models where the anti-inflammatory properties of kappa-opioid agonists have not been studied yet.
{"title":"Models of neuroinflammation for the assessment of kappa-opioid receptor ligands","authors":"K. Kalitin, A. Spasov, O. Mukha","doi":"10.19163/2307-9266-2023-11-1-4-18","DOIUrl":"https://doi.org/10.19163/2307-9266-2023-11-1-4-18","url":null,"abstract":"The development of new drugs to combat neuroinflammation is highly relevant as it opens up possibilities for the treatment of a wide range of diseases, including Alzheimer’s disease, Parkinson’s disease, epilepsy, schizophrenia, depression, and others. Kappa-opioid agonists represent a promising class of compounds with а high potential to be used in the treatment of neurological conditions accompanied by neuroinflammation.The aim of the study was to provide a summary of the current strategies employed to evaluate the neurotropic anti-inflammatory effects of kappa-opioid ligands in laboratory animals with induced neuroinflammation.Materials and methods. The databases, such as Google Scholar, PubMed, ScienceDirect, Scopus, e-Library were used as search tools. The search comprised the following keywords and phrases in Russian and English: kappa opioids + neuroinflammation; kappa opioid receptors + neuroinflammation; neuroinflammation models; neuroinflammation models in rats, neuroinflammation models in mice. 148 relevant articles were found, 122 were included in this review.Results. Various experimental models of neuroinflammation, including chemically-induced and bacterial endotoxin-induced neuroinflammation, as well as traumatic and genetic models in mice and rats were evaluated. In addition, the strengths and limitations of each model were critically assessed to identify the most appropriate and reliable approach for investigating the relationship between neuroinflammation and signaling pathways associated with kappa-opioid receptors.Conclusion. The neurotropic anti-inflammatory activity of kappa-opioid ligands have been comprehensively described. The review discusses both experimental models where the effects of kappa-opioid agonists have been investigated, as well as the models where the anti-inflammatory properties of kappa-opioid agonists have not been studied yet.","PeriodicalId":20031,"journal":{"name":"Pharmacology & Pharmacy","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83578554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-04-28DOI: 10.19163/2307-9266-2023-11-1-48-61
A. P. Danilenko, K. S. Trunov, M. Pokrovsky, L. M. Danilenko, M. V. Korokin, O. Gudyrev, A. Khentov, N. P. Masalytina, I. A. Tatarenkova, A. V. Cherednichenko, E. V. Boeva, I. S. Koklin, E. I. Taran
From the point of view of the mechanisms for the implementation of pathogenetic links in the development of steroid-induced osteoporosis considered in the paper, the increased risk of the oxidative stress in osteoblasts, as well as the development of the vessels endothelial dysfunction of the microcirculatory bloodstream in the bone tissue, are of particular interest. They lead to the impaired bone tissue trophism and progression of osteoporosis.The aim of the study was research of the osteoprotective effects of a 3-hydroxypyridine derivatives composition on the model of steroid-induced osteoporosis.Materials and methods. To model osteoporosis pathology, the animals (male Wistar rats) were injected with methylprednisolone (MP) at the dose of 5 mg/kg (intraperitoneally) every 5th day for 5 weeks. Аs a non-selective blocker of NO synthase, L-NAME was used at the dose of 25 mg/kg (intraperitoneally). Derivatives of 3-hydroxypyridine (hereinafter referred to as composition No. 1) were administrated at the dose of 50 mg/kg (per os) In all experimental groups, the level of microcirculation and the bone mineral density, as well as the analysis of histomorphological and biochemical samples, were assessed.Results. The study results showed that composition No. 1 (50 mg/kg) has an osteoprotective activity, effectively prevents a decrease in the level of the regional bone tissue microcirculation and in the development of an endothelial dysfunction. That makes it possible to increase the bone mineral density and to slow down the thinning of bone trabeculae. In addition, composition No. 1 (50 mg/kg) reduces the production of reactive oxygen species and increases the NO bioavailability.Conclusion. The data obtained indicate that the studied composition of 3-hydroxypyridine derivatives is considered a promising compound for the prevention and treatment of steroid-induced osteoporosis.
{"title":"Protective role of 3-oxypyridine derivatives in rats’ steroid-induced osteoporosis associated with reduced oxidative stress and recovery of nitric oxide formation","authors":"A. P. Danilenko, K. S. Trunov, M. Pokrovsky, L. M. Danilenko, M. V. Korokin, O. Gudyrev, A. Khentov, N. P. Masalytina, I. A. Tatarenkova, A. V. Cherednichenko, E. V. Boeva, I. S. Koklin, E. I. Taran","doi":"10.19163/2307-9266-2023-11-1-48-61","DOIUrl":"https://doi.org/10.19163/2307-9266-2023-11-1-48-61","url":null,"abstract":"From the point of view of the mechanisms for the implementation of pathogenetic links in the development of steroid-induced osteoporosis considered in the paper, the increased risk of the oxidative stress in osteoblasts, as well as the development of the vessels endothelial dysfunction of the microcirculatory bloodstream in the bone tissue, are of particular interest. They lead to the impaired bone tissue trophism and progression of osteoporosis.The aim of the study was research of the osteoprotective effects of a 3-hydroxypyridine derivatives composition on the model of steroid-induced osteoporosis.Materials and methods. To model osteoporosis pathology, the animals (male Wistar rats) were injected with methylprednisolone (MP) at the dose of 5 mg/kg (intraperitoneally) every 5th day for 5 weeks. Аs a non-selective blocker of NO synthase, L-NAME was used at the dose of 25 mg/kg (intraperitoneally). Derivatives of 3-hydroxypyridine (hereinafter referred to as composition No. 1) were administrated at the dose of 50 mg/kg (per os) In all experimental groups, the level of microcirculation and the bone mineral density, as well as the analysis of histomorphological and biochemical samples, were assessed.Results. The study results showed that composition No. 1 (50 mg/kg) has an osteoprotective activity, effectively prevents a decrease in the level of the regional bone tissue microcirculation and in the development of an endothelial dysfunction. That makes it possible to increase the bone mineral density and to slow down the thinning of bone trabeculae. In addition, composition No. 1 (50 mg/kg) reduces the production of reactive oxygen species and increases the NO bioavailability.Conclusion. The data obtained indicate that the studied composition of 3-hydroxypyridine derivatives is considered a promising compound for the prevention and treatment of steroid-induced osteoporosis.","PeriodicalId":20031,"journal":{"name":"Pharmacology & Pharmacy","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78068401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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