Experimental simulation of tuberculosis and its features in rabbits under conditions of isoniazid and N'-(2-(5-((theophyline-7-yl) methyl)-4-ethyl)-1,2,4-triazole-3-ylthio)acetyl)isonicotinohydrozide

The results of morpho-biochemical studies of tuberculosis inflammation in rabbits in an experimental model with comparative isoniazid treatment and N'-(2-(5-((theophylline-7-yl)methyl)-4-ethyl-1,2,4-triazole-3-ylthio)acetyl)isonicotinohydrazide. It was found that subcutaneous administration of N'-(2-(5-((theophylline-7-yl)methyl)-4-ethyl-1,2,4-triazole-3-ylthio)acetyl)isonicotinohydrazide at a dose of 10 mg/kg body weight leads to the absence of specific and nonspecific manifestations of inflammation in the lungs, liver, kidneys and spleen. The calculated value of the drug indicates a high degree of safety N'-(2-(5-((theophylline-7-yl)methyl)-4-ethyl-1,2,4-triazole-3-ylthio)acetyl)isonicotino-hydrazide and its prospects for veterinary practice as an effective and safe tuberculocidal drug Keywords: tuberculosis, experimental model, rabbits, treatment, 1,2,4-triazole. References Alihalassa, S. (2018). Lymph node tuberculosis: Criteria for cure and optimal duration of treatment. Tuberculosis, 52, PA2691. doi: 10.1183/13993003.congress-2018.pa2691 Balasaniantc, G., & Skotnikova, N. (2017). Diaskintest at patients after successful treatment of lung tuberculosis. Tuberculosis, 50, PA2690. doi: 10.1183/1393003.congress-2017.pa2690 Bashchenko, M.I., Boiko, ?.V., Honchar, ?.F., Gutyj, B.V., Lesyk, Y.V., Ostapyuk, A.Y., Kovalchuk, ?.?., Leskiv, Kh.Ya. (2020). The effect of milk thistle, metiphen, and silimevit on the protein-synthesizing function of the liver of laying hens in experimental chronic cadmium toxicosis. Ukrainian Journal of Ecology, 10(6), 164-168. doi: 10.15421/2020_276 Bhandari, M., & Thoen, C.O. (2014). Zoonotic tuberculosis in humans, elephants, and other animals in Nepal. Zoonotic Tuberculosis, 191–195. doi: 10.1002/9781118474310.ch16 Bihdan, O., Parchenko, V., Zazharskyi, V., Fotina, T., & Davydenko, P. (2019). Studying of physico-chemical properties of 5-(2-,3-fluorophenyl)-4-((aryl-, geteryl) yliden) amino-1,2,4-triazole-3-thiols and any of their retrievalproducts. Res. J. Pharm. Biol. Chem. Sci., 10(1), 464-474. Brezvyn, O.M., Guta, Z.A., Gutyj, B.V., Fijalovych, L.M., Karpovskyi, V.I., Shnaider, V.L., Farionik, T.V., Dankovych, R.S., Lisovska, T.O., Bushuieva, I.V., Parchenko, V.V., Magrelo, N.V., Slobodjuk, N.M., Demus, N.V., Leskiv, Kh.Ya. (2021). The influence of HamekoTox on the morphological and biochemical indices of the blood of laying hens in spontaneous fumonisin toxicosis. Ukrainian Journal of Ecology, 11 (2), 249-253 doi: 10.15421/2021_107 Collins, D.M. (2001). Virulence factors of Mycobacterium bovis. Tuberculosis, 81(1-2), 97–102. doi: 10.1054/tube.2000.0255 Gebrekidan, G., Tesfaye, G., Hambisa, M. T., & Deyessa, N. (2014). Quality of Tuberculosis Care in Private Health Facilities of Addis Ababa, Ethiopia. Tuberculosis Research and Treatment, 2014, 1–9. doi: 10.1155/2014/720432 Gotsulya, ?.S., Zazhzharskiy, V.V., Davidenko, P.O., Zazhzharskaya, N.M., Kulishenko, O.M., Panasenko, O.I., Gutyj, B.V., Pryima, O.B., Mazur, I.Y., Pritsak, V.V., Drachuk, U.R., Sobolta, A.G., & Riy, M.B. (2020). Features of experimental modeling of tuberculosis in guinea pig with the participation of N'-(2-(5- ((thephylline-7'-yl)methyl)-4-R-1,2,4-triazole-3-ylthio)acethyl)isonicotinohydrazide. Ukrainian Journal of Ecology, 10(4), 191-194. doi: 10.15421/2020_187 Gutyj, B., Ostapiuk, A., Kachmar, N., Stadnytska, O., Sobolev, O., Binkevych, V., Petryshak, R., Petryshak, O., Kulyaba, O., Naumyuk, A., Nedashkivsky, V., Nedashkivska, N., Magrelo, N., Golodyuk, I., Nazaruk, N., & Binkevych, O. (2019). The effect of cadmium loading on protein synthesis function and functional state of laying hens' liver. Ukrainian Journal of Ecology, 9(3), 222-226 Gutyj, B.V., Ostapyuk, A.Y., Sobolev, O.I., Vishchur, V.J., Gubash, O.P., Kurtyak, B.M, Kovalskyi, Y.V., Darmohray, L.M., Hunchak, A.V., Tsisaryk, O.Y., Shcherbatyy, A.R., Farionik, T.V., Savchuk, L.B., Palyadichuk, O.R., Hrymak, K. (2019). Cadmium burden impact on morphological and biochemical blood indicators of poultry. Ukrainian Journal of Ecology, 9(1), 236-239 Leveri, T.H., Lekule, I., Mollel, E., Lyamuya, F., & Kilonzo, K. (2019). Predictors of Treatment Outcomes among Multidrug Resistant Tuberculosis Patients in Tanzania. Tuberculosis Research and Treatment, 2019, 1–10. doi: 10.1155/2019/3569018 Mozaffari, A. (2018). Clinical manifestation and pulmonary function test after post tuberculosis treatment. Tuberculosis, 52, PA2747. doi: 10.1183/13993003.congress-2018.pa2747 Nakaz MOZ Ukrainy «Poriadok provedennia doklinichnoho vyvchennia likarskykh zasobiv ta ekspertyzy materialiv doklinichnoho vyvchennia likarskykh zasobiv» vid 14.12.2009 r. ?944 (in Ukrainian). Palchykov, V.A., Zazharskyi, V.V., Brygadyrenko, V.V., Davydenko, P.O., Kulishenko, O.M., & Borovik, I.V. (2020). Chemical composition and antibacterial effect of ethanolic extract of Buxus sempervirens on cryogenic strains of microorganisms in vitro. Chemical Data Collections, 25, 100323. Prasad, R., & Gupta, N. (2015). Complications of Tuberculosis. Clinical Tuberculosis: Diagnosis and Treatment, 156–156. doi:10.5005/jp/books/12549_12 Slivinska, L.G., Vlizlo, V.V., Shcherbatyy, A.R., Lukashchuk, B.O., Gutyj, B.V., Drach, M.P., Lychuk, M.G., Maksymovych, I.A., Leno, M.I., Rusyn, V.I., Chernushkin, B.O., Fedorovych, V.L., Zinko, H.O., Prystupa, O.I., Yaremchuk, V.Y. (2021). Influence of heavy metals on metabolic processes in cows. Ukrainian Journal of Ecology, 11 (2), 284-291. doi: 10.15421/2021_112 Stephanov, O.V. (Ed.) (2001) Doklinichni doslidzhennia likarskikh zasobiv [Preclinical studies of medicines]. ?yiv: Avicenna (in Ukrainian). Vasylyev, D., Priimenko, B., Aleksandrova, K., Mykhalchenko, Y., Gutyj, B., Mazur, I., Magrelo, N., Sus, H., Dashkovskyy, O., Vus, U., & Kamratska, O. (2021). Investigation of the acute toxicity of new xanthine xenobiotics with noticeable antioxidant activity. Ukrainian Journal of Ecology, 11 (1), 315-318. doi: 10.15421/2021_47 Yorke, E., Atiase, Y., Akpalu, J., Sarfo-Kantanka, O., Boima, V., & Dey, I.D. (2017). The Bidirectional Relationship between Tuberculosis and Diabetes. Tuberculosis Research and Treatment, 2017, 1–6. doi: 10.1155/2017/1702578 Zazharskyi, V., Davydenko, P., Kulishenko, O., Borovik, I., Brygadyrenko, V. (2019). Antimicrobial activity of 50 plant extracts. Biosystems Diversity, 27(2), 163-169. doi: 10.15421/011922 Zazharskyi, V., Davydenko, P., Kulishenko, O., Borovik, I., Brygadyrenko, V., & Zazharska, N. (2019). Antibacterial activity of herbal infusions against Staphylococcus aureus, Staphylococcus epidermidis and Pseudomonas aeruginosa in vitro. Magyar allatorvosok lapja, 141(11), 693–704. https://univet.hu/wp-content/uploads/2019/11/MAL-2019-11_content.pdf Zazharskyi, V., Parchenko, M., Fotina, T., Davydenko, P., Kulishenko, O., Zazharskaya, N., & Borovik, I. (2019) Synthesis, structure, physicochemical properties and antibacterial activity of 1,2,4-triazoles-3-thiols and furan derivatives. Voprosy Khimii i Khimicheskoi Tekhnologii, 6, 74–82. doi: 10.32434/0321-4095-2019-127-6-74-82 Zazharskyi, V.V., Davydenko, P.?., Bigdan, O ?., Hotsulia, A.S., Kulishenko, O.?., Gutyj, B.V., Salata, V.Z., Khimych, M.S., Skrypka, H.A., Naidich, O.V., Anforova, M.V., Popova, I.M., & Franchuk-Kryva, L.O. (2020). Determination of minimum inhibitory concentration (MIC) of some 1,2,4-triazole derivatives with potential tuberculostatic and tuberculocidal ability in vitro. Ukrainian Journal of Ecology, 10(6), 145-159. doi: 10.15421/2020_274 Zijenah, L.S. (2018). The World Health Organization Recommended TB Diagnostic Tools. Tuberculosis. doi: 10.5772/intechopen.73070