The influence of new coumarin derivatives on survival rate of mice in model conditions of acute hypoxia
- Authors: Rodionova O.M.1, Safonova A.F.1, Kashirin A.O.1, Polukeev V.A.1, Bychkov E.R.1, Lebedev A.A.1, Shabanov P.D.1,2
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Affiliations:
- Institute of Experimental Medicine
- S.M. Kirov Military Medical Academy
- Issue: Vol 19, No 4 (2019)
- Pages: 103-108
- Section: Original research
- Published: 03.04.2020
- URL: https://journals.eco-vector.com/MAJ/article/view/19258
- DOI: https://doi.org/10.17816/MAJ19258
- ID: 19258
Cite item
Abstract
Objective. The article is devoted to study the anti-hypoxemic properties of new coumarin derivatives in the models of hypoxemic hypoxia with hypercapnia, hemic hypoxia and histotoxic hypoxia.
Materials and methods. Нypoxemic hypoxia with hypercapnia was modeled as follows: mice were placed in hermetic 200 cm3 jars one in a jar. Hemic hypoxia was reproduced in mice by single subcutaneous introduction of sodium nitrite in a dose of 230 mg/kg. Histotoxic hypoxia was caused in mice by intraperitoneal introduction of sodium nitroprusside in a dose of 20 mg/kg. Coumarin derivatives under lab codes IEM-2266 and IEM-2267 were dissolved in distilled water with addition of twin-80, and then a single intraperitoneal infusion of them in doses 25 and 50 mg/kg was made 45 minutes before placing to the model conditions. Increased life time of an animal compared with the control served the criterion of anti-hypoxemic effect of the studied substances.
Results. In hypoxemic hypoxia with hypercapnia test compound under IEM-2267 in doses of 25 and 50 mg/kg increased mice life time by 26 and 34% respectively in comparison with control. In hemic hypoxia model, the positive effect was seen with IEM-2266 compound in a dose of 50 mg/kg which increased life time of animals by 45% in comparison with control. In histotoxic hypoxia model, at preventive introduction of IEM-2266 compound in a dose of 25 mg/kg and IEM-2267 in a dose of 50 mg/kg life time increased up to 117% and 123% respectively.
Conclusion. The coumarin derivatives IEM-2266 and IEM-2267 relieved the course of acute hypoxia and increased life time of animals in the models of hypoxemic hypoxia with hypercapnia, hemic hypoxia and histotoxic hypoxia.
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About the authors
Olga M. Rodionova
Institute of Experimental Medicine
Email: 31olga59@mail.ru
PhD, Scientific Researcher, S.V. Anichkov Department of Neuropharmacology
Russian Federation, Saint PetersburgAlbina F. Safonova
Institute of Experimental Medicine
Email: safonova@list.ru
Scientific Researcher, S.V. Anichkov Department of Neuropharmacology
Russian Federation, Saint PetersburgAnton O. Kashirin
Institute of Experimental Medicine
Email: kashirin.anton@mail.ru
PhD student, S.V. Anichkov Department of Neuropharmacology
Russian Federation, Saint PetersburgValeriy A. Polukeev
Institute of Experimental Medicine
Email: cyclic@peterlink.ru
Scientific Researcher, S.V. Anichkov Department of Neuropharmacology
Russian Federation, Saint PetersburgEugenii R. Bychkov
Institute of Experimental Medicine
Author for correspondence.
Email: bychkov@mail.ru
PhD, Head of The Laboratory of Chemistry and Pharmacology of Pharmaceutical Drug of S.V. Anichkov Department of Neuropharmacology
Russian Federation, Saint PetersburgAndrei A. Lebedev
Institute of Experimental Medicine
Email: aalebedev-iem@rambler.ru
PhD, Dr Biol Sci, Professor, Head of The Laboratory of General Pharmacology of S.V. Anichkov Department of Neuropharmacology
Russian Federation, Saint PetersburgPetr D. Shabanov
Institute of Experimental Medicine; S.M. Kirov Military Medical Academy
Email: pdshabanov@mail.ru
ORCID iD: 0000-0003-1464-1127
Dr. Med. Sci. (Pharmacology), Professor and Head, Dept. of Neuropharmacology; Head, Department of Pharmacology
Russian Federation, Saint PetersburgReferences
- Зарубина И.В. Современные представления о патогенезе гипоксии и ее фармакологической коррекции // Обзоры по клинической фармакологии и лекарственной терапии. – 2011. – Т. 9. – № 3 – С. 31–48. [Zarubina IV. Modern view on pathogenesis of hypoxia and its pharmacological corection. Reviews on Clinical Pharmacology and Drug Therapy. 2011;9(3):31-48. (In Russ.)]
- Шабанов П.Д., Зарубина И.В., Новиков В.Е., Цыган В.Н. Метаболические корректоры гипоксии. – СПб., 2010. [Shabanov PD, Zarubina IV, Novikov VE, Tsygan VN. Metabolic hypoxia correctors. Saint Petersburg; 2010. (In Russ.)]
- Kostova I. Synthetic and natural coumarins as cytotoxic agents. Curr Med Chem Anticancer Agents. 2005;5(1):29-46. https://doi.org/10.2174/1568011053352550.
- Hu XL, Xu Z, Liu ML, et al. Recent developments of coumarin hybrids as anti-fungal agents. Curr Top Med Chem. 2017;17(29):3219-3231. https://doi.org/10.2174/1568026618666171215100326.
- Bibak B, Shakeri F, Barreto GE, et al. A review of the pharmacological and therapeutic effects of auraptene. Biofactors. 2019;45(6):867-879. https://doi.org/10.1002/biof.1550.
- Лукьянова Л.Д. Современные подходы к поиску антигипоксантов // Актуальные проблемы фармакологии и поиска новых лекарственных препаратов. Т. 10. Материалы конференции, посвященной 15-летию НИИ фармакологии. – Томск, 1999. – С. 59–67. [Luk’yanova LD. Sovremennye podkhody k poisku antigipoksantov. In: Aktual’nye problemy farmakologii i poiska novykh lekarstvennykh preparatov. Vol. 10. Materialy konferentsii, posvyashchennoy 15-letiyu NII farmakologii. Tomsk; 1999. P. 59-67. (In Russ.)]
- Руководство по проведению доклинических исследований лекарственных средств. Часть первая / под ред. А.Н. Миронова. – М.: Гриф и К, 2012. [Rukovodstvo po provedeniyu doklinicheskikh issledovaniy lekarstvennykh sredstv. Chast’ pervaya. Ed. by A.N. Mironov. Moscow: Grif &Co; 2012. (In Russ.)]
- Лукьянова Л.Д. Антигипоксанты, подходы к их классификации, принципы применения // Фармакологическая коррекция гипоксических состояний. – Гродно, 1991. – С. 126–127. [Luk’yanova LD. Antigipoksanty, podkhody k ikh klassifikatsii, printsipy primeneniya. In: Farmakologicheskaya korrektsiya gipoksicheskikh sostoyaniy. Grodno; 1991. P. 126-127. (In Russ.)]
- Сафонова А.Ф., Бурбелло А.Т. Экспериментальный анализ действия новых производных пиримидина при токсическом отеке легких // Медико-биологические проблемы современного промышленного производства. – Л.: ЛСГМИ, 1990. – С. 19–23. [Safonova AF, Burbello AT. Eksperimental’nyy analiz deystviya novykh proizvodnykh pirimidina pri toksicheskom oteke legkikh. In: Mediko-biologicheskie problemy sovremennogo promyshlennogo proizvodstva. Leningrad: LSGMI; 1990. P. 19-23. (In Russ.)]
- Островский О.В. Фармакология антиоксидантов: Автореф. дис. … д-ра мед. наук. – Волгоград, 1995. [Ostrovskiy OV. Farmakologiya antioksidantov. [dissertation] Volgograd; 1995. (In Russ.)]
- Лукьянова Л.Д. Фармакологические эффекты биоэнергетики // Клеточные механизмы реализации фармакологического эффекта. – М., 1990. – С. 184-216. [Luk’yanova LD. Farmakologicheskie effekty bioenergetiki. In: Kletochnye mekhanizmy realizatsii farmakologicheskogo effekta. Moscow; 1990. P. 184-216. (In Russ.)]
- Debeljak Z, Skrbo A, Jasprica I, et al. QSAR study of antimicrobial activity of some 3-nitrocoumarins and related compounds. J Chem Inf Model. 2007;47(3):918-926. https://doi.org/10.1021/ci600473z.
- Mokrov GV, Savel’ev VL, Voronina TA, et al. Synthesis and Anticonvulsant Activity of N-Substituted 4-Amino-3-Nitrocoumarins. Pharm Chem J. 2019;53(2):118-124. https://doi.org/10.1007/s11094-019-01964-7.
- Руководство по экспериментальному (доклиническому) изучению новых фармакологических веществ / под ред. Р.У. Хабриева. – М.: Медицина, 2005. [Rukovodstvo po eksperimental’nomu (doklinicheskomu) izucheniyu novykh farmakologicheskikh veshchestv. Ed. by R.U. Khabriev. Moscow: Izdatel’stvo Meditsina; 2005. (In Russ.)]
- Savel’ev VL, Pryanishnikova NT, Artamonova OS, et al. Synthesis and pharmacological activity of 4-amino-3-nitrocoumarins. Pharm Chem J. 1975;9(6):360-362. https://doi.org/10.1007/bf00758772.
- Arieli R, Kwetny I. Effect of diazepam on survival of the immature pig in a confined atmosphere. J Basic Clin Physiol Pharmacol. 1999;10(1):15-27. https://doi.org/10.1515/ jbcpp.1999.10.1.15.
- Бурбелло А.Т. Производные барбитуровой кислоты – новый класс соединений для профилактики и лечения отравлений нитросоединениями: Автореф. дис. … д-ра мед. наук. – СПб., 1991. [Burbello AT. Proizvodnye barbiturovoy kisloty – novyy klass soedineniy dlya profilaktiki i lecheniya otravleniy nitrosoedineniyami. [dissertation] Saint Petersburg; 1991. (In Russ.)]
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