DOI: https://doi.org/10.24959/ubphj.19.222

Study of hepatoprotective effect of a new herbal remedy “Hepatropin” on a model of hepatitis in rats caused by tuberculostatic medicines

O. V. Gerysh, L. V. Iakovlieva

Abstract


Topicality. It is known that anti-tuberculosis (TB) drugs is hapatotoxic. Treatment of patients with tuberculosis involves the use of anti-TB drugs (4-6) complex at the same time, which causes the development of severe toxic hepatitis. Severe toxic hepatitis occurs during the treatment of first-line drugs in 60 % of patients and 42.4 % when used of second-line drugs. In 10-28 % of patients the development of severe hepatitis requires the abolition of anti-TB chemotherapy. The existing conditions require the search and creation of new herbal drugs for the prevention and treatment of hepatitis caused by drugs

Aim. To evaluate the effectiveness of a new complex herbal medicine (CHM) “Hepatropin” in the form of granules in the experimental hepatitis conditions caused by tuberculostatic drugs.

Materials and methods. Study of hepatoprotective activity of a new CHM, “Hepatropin” granules (intragastrically 900 mg/kg once a day) on a model of hepatitis caused by intragastric administration  of tuberculostatics mixture (Isoniazid 50 mg/kg, Rifampin 500 mg/kg, Pyrazynamide 1500 mg/kg) in the form of  aqueous suspension for 14 days, in comparison with a reference medicine containing extracts of Fumaria officinalis and Silybum marianum fruits (intragastrically 35 mg/kg once a day). To assess the general condition of the animals, their survival was assessed; for the assessment of the functional state of the liver, the activity of the enzymes alanine aminotransferase (AlAT), alkaline phosphatase (APh), liver mass coefficient (LMC) were determined in the serum. The processes intensity of lipid peroxidation (LPO) and  the antioxidant system activity (AAS) was evaluated in accordance with the TBA-active products level (TBA-AP), reduced glutathione (RG) in serum and the activity of the antioxidative enzyme catalase in the liver homogenate. The state of lipid metabolism was assessed by the cholesterol level and total lipids in serum.

Results and discussions. Granules “Hepatropin” contributed to a decrease in LMC from 4.02 % to 3.66 % and alkaline phosphatase activity 1.4 times, AlAT 1.6 times in serum, TBA-AP 1.4 times, increased level of RG in the homogenate liver and catalase in the blood serum, respectively, 1.7 and 1.9 times, as well as a decrease in the level of total lipids and cholesterol in the blood serum, respectively, 2.2 and 3.6 times relative to similar indicators in untreated animals.

Conclusions. The hepatoprotective effect of the herbal medicine “Hepatropin” has been established. The severity of normalizing effect on the disturbed lipids level in the serum, pro- and antioxidant balance. According to indicators, the drug “Hepatropin” exceeded the effect of the reference drug. The presence of a pronounced hepatoprotective action justifies the further expediency study with the aim of practical “Hepatropin” agent application for the correction of the hepatotoxic effects of anti-tuberculosis drugs.


Keywords


experimental hepatitis caused by tuberculostatic drugs; herbal medicines; hepatoprotective activi

References


1. Ivanova, D. A., Borisov, S. E., Ryzhov, A. M., Ivanushkina, T. N. (2013). Tuberkulez i bolezni legkih, 11(90), 25–31.

2. Sukhanov, D. S. (2014). Farmakoterapiia lekarstvennykh porazhenii pecheni pri tuberkuleze (eksperimentalno-klinicheskoe issledovanie). Doctor’s thesis. St-Peterburgskaia gosudarstvennaia meditcinskaia akademiia im. I. I. Mechnikova Federalnogo agentstva po zdravookhraneniiu i sotcialnomu razvitiiu. St-Petersburg, 273.

3. Naqvi, I. H., Mahmood, K., Talib, A., & Mahmood, A. (2015). Antituberculosis Drug-Induced Liver Injury: An Ignored Fact, Assessment of Frequency, Patterns, Severity and Risk Factors. Open Journal of Gastroenterology, 5(12), 173–184. https://doi.org/10.4236/ojgas.2015.512027

4. Shang, P., Xia, Y., Liu, F., Wang, X., Yuan, Y., Hu, D., … Zhan, S. (2011). Incidence, Clinical Features and Impact on Anti-Tuberculosis Treatment of Anti-Tuberculosis Drug Induced Liver Injury (ATLI) in China. PLoS ONE, 6(7), e21836. https://doi.org/10.1371/journal.pone.0021836

5. Ramappa, V., & Aithal, G. P. (2013). Hepatotoxicity Related to Anti-tuberculosis Drugs: Mechanisms and Management. Journal of Clinical and Experimental Hepatology, 3(1), 37–49. https://doi.org/10.1016/j.jceh.2012.12.001

6. Kharchenko, N. V., Anokhin, G. A., Chekman, S. I., Korulya, I. A., Kharchenko, V. V. (2013). Zdorov’ia Ukrainy, 1(27), 28–29.

7. Herush O. V., Yakovlieva L. V., Lar’ianovska Yu. B., Sakharova T. S. (2015). Ukraïns’kij bìofarmacevtičnij žurnal, 2 (37),44–48.

8. Iakovlieva, L. V., Gerush, O. V., Laryanovskaya, Yu. B., Spiridonov, S. V., Mishchenko, O. Ya. (2016). Universum: Meditcina i farmakologiia : elektronnyi nauchnyi zhurnal, 10 (32). Available at: http://7universum.com/ru/med/archive/item/3761

9. Iakovlieva, L. V., Herush, O. V., Spiridonov, S. V. (2011). Vіsnik farmacії, 3(67), 70–73.

10. Ulanova, I. P., Sidorov, K. K., Khalepo, A. I. (1968). K voprosu ob uchete poverkhnosti tela eksperimentalnykh zhivotnykh pri toksikologicheskom issledovanii. Leningrad : Meditcina, 10, 18–25.

11. Stefanov, O. V. (2001). Doklinichni doslidzhennia likarskykh zasobiv: Metodychni rekomendatsii. Kyiv: Avitsena, 528.

12. Fisenko, V. P. (Ed). (2000). Rukovodstvo po eksperimentalnomu (doklinicheskomu) izucheniiu novykh farmakologicheskikh veshchestv. Moscow: Remedium, 349–354.


GOST Style Citations


1. Частота, характер и факторы риска лекарственно-индуцированного поражения печени при лечении впервые выявленных больных туберкулёзом / Д. А. Иванова, С. Е. Борисов, А. М. Рыжов, Т. Н. Иванушкина // Туберкулез и болезни легких. – 2013. – № 11 (90). – С. 25–31.

2. Суханов, Д. С. Фармакотерапия лекарственных поражений печени при туберкулезе (экспериментально-клиническое исследование): дис. … д-ра. мед. наук : 14.01.16 / Санкт-Петербургская государственная медицинская академия им. И. И. Мечникова Федерального агентства по здравоохранению и социальному развитию. Санкт-Петербург, 2014. 273 с.

3. Antituberculosis drug-induced liver injury: an ignored fact, assessment of frequency, patterns, severity and risk factors / I. Naqvi, K. Mahmood, A. Talib, A. Mahmoo // Open Journal of Gastroenterology. – 2015. – № 5. – P. 173–184. https://doi.org/10.4236/ojgas.2015.512027 

4. Incidence, Clinical Features and Impact on Anti-Tuberculosis Treatment of Anti-Tuberculosis Drug Induced Liver Injury (ATLI) in China / P. Shang, Y. Xia, F. Liu, [et al.] // PLoS ONE. – 2011. – Vol. 6 (7). https://doi.org/10.1371/journal.pone.0021836 

5.Ramappa, V. Hepatotoxicity related to anti-tuberculosis drugs: mechanisms and management / V. Ramappa, G. P. Aithal // J. Clin. Exp. Hepatol. – 2013. – Vol. 3 (1). – P. 37–49.https://doi.org/10.1016/j.jceh.2012.12.001 

6. Гепатопротектори в лікуванні захворювань печінки: клініко-біохімічні механізми дії / Н. В. Харченко [та ін.] // Здоров’я України. – 2013. – № 1 (27). С. 28–29.

7. Експериментальне вивчення гранул «Гепатотропин» як потенційного гепатотропного засобу / О. В. Геруш, Л. В. Яковлєва, Ю. Б. Лар’яновська, Т. С. Сахарова // Український біофармацевтичний журнал. – 2015. – № 2 (37). – С. 44–48.

8. Исследование влияния гранул «Гепатропин» на течение хронического экспериментального гепатита / Л. В. Яковлева [и др.] // Universum: Медицина и фармакология : электрон. научн. журн. – 2016. – № 10 (32). – Режим доступу : http://7universum.com/ru/med/archive/item/3761 (дата обращения: 08.02.2019).

9. Дослідження гепатозахисної дії нового рослинного засобу «ШКТ-2» / Л. В. Яковлєва [та ін.] // Вісник фармації. – 2011. – №3 (67). – С. 70–73.

10. Уланова, И. П. K вопросу об учете поверхности тела экспериментальных животных при токсикологическом исследовании / И. П. Уланова, К. К. Сидоров, А. И. Халепо. – Ленинград : Медицина, 1968. – Вып. 10. – С. 18–25.

11. Доклінічні дослідження лікарських засобів: метод. рекоменд. / За ред. чл.-кор. НАМН України О. В. Стефанова. Київ : Авіценна, 2001. – 528 с.

12. Руководство по экспериментальному (доклиническому) изучению новых фармакологических веществ / под ред. В. П. Фисенко. Москва : Ремедиум, 2000. – С. 349–354.





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