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Evaluation of Toxic Properties of New Glycopeptide Flavancin on Rats

Glycopeptide antibiotics have side effects that limit their clinical use. In view of this, the development of glycopeptides with improved chemotherapeutic properties remains the main direction in the search for new antibacterial drugs. The objective of this study was to evaluate the toxicological ch...

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Autores principales: Treshchalin, Michael I., Polozkova, Vasilisa A., Moiseenko, Elena I., Treshalina, Helen M., Shchekotikhin, Andrey E., Pereverzeva, Eleonora R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9228439/
https://www.ncbi.nlm.nih.gov/pubmed/35745578
http://dx.doi.org/10.3390/ph15060661
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author Treshchalin, Michael I.
Polozkova, Vasilisa A.
Moiseenko, Elena I.
Treshalina, Helen M.
Shchekotikhin, Andrey E.
Pereverzeva, Eleonora R.
author_facet Treshchalin, Michael I.
Polozkova, Vasilisa A.
Moiseenko, Elena I.
Treshalina, Helen M.
Shchekotikhin, Andrey E.
Pereverzeva, Eleonora R.
author_sort Treshchalin, Michael I.
collection PubMed
description Glycopeptide antibiotics have side effects that limit their clinical use. In view of this, the development of glycopeptides with improved chemotherapeutic properties remains the main direction in the search for new antibacterial drugs. The objective of this study was to evaluate the toxicological characteristics of new semi-synthetic glycopeptide flavancin. Acute and chronic toxicity of antibiotic was evaluated in Wistar rats. The medium lethal dose (LD(50)) and the maximum tolerated doses (MTD) were calculated by the method of Litchfield and Wilcoxon. In the chronic toxicity study, the treatment regimen consisted of 15 daily intraperitoneal injections using two dosage levels: 6 and 10 mg/kg/day. Total doses were equivalent to MTD or LD(50) of flavancin, respectively. The study included assessment of the body weight, hematological parameters, blood biochemical parameters, urinalysis, and pathomorphological evaluation of the internal organs. The results of the study demonstrated that no clinical-laboratory signs of toxicity were found after 15 daily injections of flavancin at a total dose close to the MTD or LD(50). The pathomorphological study did not reveal any lesions on the organ structure of animals after low-dose administration of flavancin. Thus, flavancin favorably differs in terms of toxicological properties from the glycopeptides currently used in the clinic.
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spelling pubmed-92284392022-06-25 Evaluation of Toxic Properties of New Glycopeptide Flavancin on Rats Treshchalin, Michael I. Polozkova, Vasilisa A. Moiseenko, Elena I. Treshalina, Helen M. Shchekotikhin, Andrey E. Pereverzeva, Eleonora R. Pharmaceuticals (Basel) Article Glycopeptide antibiotics have side effects that limit their clinical use. In view of this, the development of glycopeptides with improved chemotherapeutic properties remains the main direction in the search for new antibacterial drugs. The objective of this study was to evaluate the toxicological characteristics of new semi-synthetic glycopeptide flavancin. Acute and chronic toxicity of antibiotic was evaluated in Wistar rats. The medium lethal dose (LD(50)) and the maximum tolerated doses (MTD) were calculated by the method of Litchfield and Wilcoxon. In the chronic toxicity study, the treatment regimen consisted of 15 daily intraperitoneal injections using two dosage levels: 6 and 10 mg/kg/day. Total doses were equivalent to MTD or LD(50) of flavancin, respectively. The study included assessment of the body weight, hematological parameters, blood biochemical parameters, urinalysis, and pathomorphological evaluation of the internal organs. The results of the study demonstrated that no clinical-laboratory signs of toxicity were found after 15 daily injections of flavancin at a total dose close to the MTD or LD(50). The pathomorphological study did not reveal any lesions on the organ structure of animals after low-dose administration of flavancin. Thus, flavancin favorably differs in terms of toxicological properties from the glycopeptides currently used in the clinic. MDPI 2022-05-25 /pmc/articles/PMC9228439/ /pubmed/35745578 http://dx.doi.org/10.3390/ph15060661 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Treshchalin, Michael I.
Polozkova, Vasilisa A.
Moiseenko, Elena I.
Treshalina, Helen M.
Shchekotikhin, Andrey E.
Pereverzeva, Eleonora R.
Evaluation of Toxic Properties of New Glycopeptide Flavancin on Rats
title Evaluation of Toxic Properties of New Glycopeptide Flavancin on Rats
title_full Evaluation of Toxic Properties of New Glycopeptide Flavancin on Rats
title_fullStr Evaluation of Toxic Properties of New Glycopeptide Flavancin on Rats
title_full_unstemmed Evaluation of Toxic Properties of New Glycopeptide Flavancin on Rats
title_short Evaluation of Toxic Properties of New Glycopeptide Flavancin on Rats
title_sort evaluation of toxic properties of new glycopeptide flavancin on rats
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9228439/
https://www.ncbi.nlm.nih.gov/pubmed/35745578
http://dx.doi.org/10.3390/ph15060661
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