Acute toxicity study of a new dibenzofuran oxime derivative GIZH-272 in mice
S. V. Alekseeva,
A. V. Sorokina,
A. V. . Volkova,
I. A. Miroshkina,
K. S. Kachalov,
I. V. Alekseev,
A. D. Zakharov,
A. D. Durnev https://doi.org/10.37489/2587-7836-2023-4-63-69
Abstract
Relevance. Acute toxicity testing is a common procedure for preclinical safety testing of potential agents. The purpose of this study was to study the acute toxicity of the compound GIZH-272, a new dibenzofuran oxime derivative with anti-ischemic and anticonvulsant effects. Methods. The compound was administered to mice intraperitoneally and orally once. Within 14 days, the condition of the animals was monitored, clinical manifestations of intoxication were recorded, and changes in the dynamics of body weight and its growth were recorded. Results. It was found that the test compound at maximum doses did not lead to the death of mice. Therefore, the data obtained according to the classification of Sidorov K.K. (1973), make it possible to attribute GIZH-272 to the 5th class of toxicity — "practically non-toxic substance". In accordance with GOST 12.1.007-76, the GIZH-272 compound belongs to the 4th hazard class (low-hazard substance) for oral administration.
About the Authors
S. V. Alekseeva
Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies
Russian Federation
Russian Federation
Svetlana V. Alekseeva - Senior researcher of the laboratory of drug toxicology
Moscow
A. V. Sorokina
Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies
Russian Federation
Russian Federation
Alexandra V. Sorokina - PhD, Cand. Sci. (Biology), leading researcher of the laboratory of drug toxicology
Moscow
A. V. . Volkova
Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies
Russian Federation
Russian Federation
Anna V. Volkova -Senior researcher of the laboratory of psychopharmacology
Moscow
I. A. Miroshkina
Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies
Russian Federation
Russian Federation
Irina A. Miroshkina - Researcher scientist of the laboratory of drug toxicology
Moscow
K. S. Kachalov
Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies
Russian Federation
Russian Federation
Kirill S. Kachalov - Junior researcher of the laboratory of drug toxicology
Moscow
I. V. Alekseev
Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies
Russian Federation
Russian Federation
Ivan V. Alekseev - engineer of the laboratory of pharmacology of Mutagenesis
Moscow
A. D. Zakharov
Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies
Russian Federation
Russian Federation
Aleksey D. Zakharov - Junior researcher of the laboratory of drug toxicology
Moscow
A. D. Durnev
Federal Research Center for Innovator and Emerging Biomedical and Pharmaceutical Technologies
Russian Federation
Russian Federation
Andrei D. Durnev - Dr. Sci. (Med.), professor, corresponding member RAS, Head of the department of drug toxicology
Moscow
References
1. Кутепова И.С., Литвинова С.А., Воронина Т.А., и др. Противосудорожная активность производных дибензофурана в эксперименте. Экспериментальная и клиническая фармакология. 2019;82(8):3–8. DOI: 10.30906/0869-2092-2019-82-8-3-8. Kutepova IS, Litvinova SA, Voronina TA, et al. Anticonvulsant activity of dibenzofuran derivatives: experimental screening. Exper Clin Pharmacol. 2019;82(8):3-8. (In Russ.). DOI: 10.30906/0869-2092-2019-82-8-3-8.
2. Литвинова С.А., Кутепова И.С., Курза Е.В., и др. Противоишемические и цереброваскулярные свойства производного оксима дибензофурана ГИЖ-272. Экспериментальная и клиническая фармакология. 2019;82(6):3–7. DOI: 10.30906/0869-2092-2019-82-6-3-7. Litvinova SA, Kutepova IS, Kurza EV, et al. Anti-ischemic and cerebrovascular properties of dibenzofuran oxime derivative GIZh-272. Exper Clin Pharmacol. 2019;82(6):3–7. (In Russ.). DOI: 10.30906/0869-2092-2019-82-6-3-7.
3. Кутепова И.С., Литвинова С.А., Воронина Т.А., Жмуренко Л.А. Исследование нового производного оксима дибензофурана ГИЖ-272 на моделях очаговой эпилепсии и интрацеребральной посттравматической гематомы. Экспериментальная и клиническая фармакология. 2020;83(9):3–8. DOI: 10.30906/0869-2092-2020-83-9-3-8. Kutepova IS, Litvinova SA, Voronina TA, Zhmurenko LA. Studying new dibenzofuran oxime derivative GIZh-272 on the models of focal epilepsy and intracerebral post-traumatic hematoma. Exper Clin Pharmacol. 2020;83(9):3–8. (In Russ.). DOI: 10.30906/0869-2092-2020-83-9-3-8.
4. Руководство по проведению доклинических исследований лекарственных средств. Ч. 1. Методические рекомендации по изучению общетоксического действия лекарственных средств. Изучение острой токсичности. М.: Гриф и К, 2012. С. 15-17. Guidelines for conducting preclinical studies of medicines. Part 1. Methodological recommendations for the study of the general toxic effect of medicines. Study of acute toxicity. Moscow: Grif i K; 2012. (In Russ.).
5. Правила доклинической оценки безопасности фармакологических средств. РД 64-126-91. М.: МЗ России, ФК; 1992. Rules of preclinical safety assessment of pharmacological agents. RD 64-126-91. Moscow: Ministry of Health of Russia, FC; 1992 (In Russ.).
6. Руководство по экспериментальному (доклиническому) изучению новых фармакологических веществ. Методические указания по изучению общетоксического действия фармакологических веществ. М.: Медицина, 2005. С. 41–47. Guidelines for experimental (preclinical) study of new pharmacological substances. Methodological guidelines for the study of the general toxic effect of pharmacological substances. Moscow: Medicine, 2005. (In Russ.).
7. Проблема нормы в токсикологии [Текст] : (современные представления и метод. подходы, основные параметры и константы) / И.М. Трахтенберг, Р.Е. Сова, В.О. Шефтель, Ф.А. Оникиенко; под ред. И.М. Трахтенберга. 2-е изд., перераб. и доп. М.: Медицина, 1991. 203. Problema normy v toksikologii [Tekst] : (sovremennye predstavleniya i metod. podhody, osnovnye parametry i konstanty). IM Trahtenberg, RE Sova, VO SHeftel', FA Onikienko; Ed. by IM Trahtenberga. Moscow: Medicine, 1991. (In Russ.).
8. Экстраполяция токсикологических данных с животных на человека / Г.Н. Красовский, Ю.А. Рахманин, Н.А. Егорова. М.: Медицина, 2009. 206. Ekstrapolyaciya toksikologicheskih dannyh s zhivotnyh na cheloveka / GN Krasovskij, YuA Rahmanin, NA Egorova. Moscow: Medicina, 2009. (In Russ.).
9. Guide for the Care and Use of Laboratory Animals. National Academies Press (US). Washington (DC). 2011. DOI: 10.17226/12910.
10. Березовская И.В. Классификация химических веществ по параметрам острой токсичности при парентеральных способах введения. Химико-фармацевтический журнал. 2003;37(3):32–34. Berezovskaya IV. Classification of chemicals according to the parameters of acute toxicity in parenteral methods of administration. Chemical and pharmaceutical journal. 2003;37(3):32–34. (In Russ.).
Review
For citations:
Alekseeva S.V., Sorokina A.V., Volkova A.V., Miroshkina I.A., Kachalov K.S., Alekseev I.V., Zakharov A.D., Durnev A.D. Acute toxicity study of a new dibenzofuran oxime derivative GIZH-272 in mice. Pharmacokinetics and Pharmacodynamics. 2023;(4):63-69. (In Russ.) https://doi.org/10.37489/2587-7836-2023-4-63-69
Views:
329
Email this article 