Email this article PRECLINICAL STUDY OF SUBCHRONIC TOXICITY OF THE DRUG ON THE BASIS OF ACADESINE IN RATS
- Authors: Ermakova N.Р.1, Merkulova I.B.1, Konyaeva O.I.1, Chaley V.A.1, Abramova T.V.1, Bukhman V.M.1, Yarotsky S.V.2, Lobanov K.V.2, Kulbachevskaya N.Y.1
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Affiliations:
- N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation
- State Research Institute of Genetics and Selection of Industrial Microorganisms of the National Research Center “Kurchatov Institute”
- Issue: Vol 19, No 2 (2020)
- Pages: 65-73
- Section: ORIGINAL REPORTS
- Published: 18.06.2020
- URL: https://bioterapevt.abvpress.ru/jour/article/view/1205
- DOI: https://doi.org/10.17650/1726-9784-2019-19-2-65-73
- ID: 1205
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Abstract
Introduction At the national medical research center of оncology N.N. Blokhin preclinical toxicological studies of a lyophilized dosage form of a drug based on acadesin, a new antitumor drug, were conducted.
The aim of the study to study the subchronic toxicity of the drug on the basis of acadesine in rats to evaluate its toxicity.
Materials and methods The study was conducted on 40 noninbred male mongrel rats. The drug was administered intraperitoneal daily 15-fold in total doses of 750, 1150 and 2300 mg/kg. Clinical and laboratory tests were performed during the entire observation period (30 days). The pathomorphological study was performed on the 1st and 30 th day of observation.
Results It was found that the drug based on acadesin, when applied repeatedly to rats in all the studied doses, did not cause changes in the indicators of peripheral blood of animals, morphological changes in all the studied organs and tissues of animals (except the kidneys), functional changes in the state of the liver, heart, kidneys and gastrointestinal tract. However, morphologically revealed changes in the kidneys when using the drug in the total dose of 1150 mg/kg on the 1st and 30 th day of observation, and in the total dose of 2300 mg/kg only on the 30 th day of observation.
Conclusion The detected toxic effect of the drug based on acadesin on the kidneys of rats is dose-dependent. When using the drug in the course of the course at a total dose of 750 mg/kg, which is 60 times higher than the single therapeutic dose for rats (12.5 mg/kg), toxic manifestations were completely absent during the entire period of observation. This allowed us to recommend a drug based on acadesin for further research.
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About the authors
N. Р. Ermakova
N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation
Author for correspondence.
Email: ne518@yandex.ru
24 Kashirskoe Shosse, Moscow 115478
Russian Federation
I. B. Merkulova
N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation
ORCID iD: 0000-0001-7461-3422
24 Kashirskoe Shosse, Moscow 115478 Russian Federation
O. I. Konyaeva
N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation
ORCID iD: 0000-0002-3814-5630
24 Kashirskoe Shosse, Moscow 115478 Russian Federation
V. A. Chaley
N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation
ORCID iD: 0000-0001-7867-2868
24 Kashirskoe Shosse, Moscow 115478 Russian Federation
T. V. Abramova
N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation24 Kashirskoe Shosse, Moscow 115478 Russian Federation
V. M. Bukhman
N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation
ORCID iD: 0000-0002-7062-798X
24 Kashirskoe Shosse, Moscow 115478 Russian Federation
S. V. Yarotsky
State Research Institute of Genetics and Selection of Industrial Microorganisms of the National Research Center “Kurchatov Institute”
1 1st Dorozhniy proezd, Moscow 117545
Russian Federation
K. V. Lobanov
State Research Institute of Genetics and Selection of Industrial Microorganisms of the National Research Center “Kurchatov Institute”1 1st Dorozhniy proezd, Moscow 117545 Russian Federation
N. Yu. Kulbachevskaya
N.N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of the Russian Federation
ORCID iD: 0000-0003-4214-3475
24 Kashirskoe Shosse, Moscow 115478 Russian Federation
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