Morphological changes in parenchymal organs of laboratory animals in acute effect of carbon tetrachloride

封面

如何引用文章

全文:

详细

Introduction. Among noninfectious diseases, one of the leading places belongs to pathologies caused by the action of industrial toxicants. In this regard, the search for drugs for the prevention and treatment of various intoxications is one of the priority tasks of public health. Treatment of intoxication with drugs with antioxidant and antihypoxic activity is more effective.

The aim of this study was to investigate morphological changes in parenchymal organs (liver, kidneys, and pancreas) under acute exposure to high doses of carbon tetrachloride and to evaluate the effectiveness of their correction with a new composition of oxymethyluracil with ascorbic acid.

Material and methods. The composition of 5-hydroxy-6-methyluracil with ascorbic acid was first synthesized at the Ufa Institute of Chemistry, Ufa Federal Research Center, RAS. The preventive effect of the new drug was studied in comparison with “Heptor” on the carbon tetrachloride-induced liver injury model. Morphological studies of the liver, pancreas, and kidneys of laboratory animals were carried out.

Results. Studies have shown the prophylactic administration of new composition of 5-hydroxy-6-methyluracil with ascorbic acid to have a protective effect on the structure of parenchymal organs in acute carbon tetrachloride intoxication, comparable to the drug “Heptor” (possibly superior). However, reparative properties were observed only in the drug “Heptor”.

Conclusion. Comparative estimation of morphological changes in parenchymal organs under acute exposure to high doses of carbon tetrachloride indicates the protective effect of prophylactic administration of the composition of 5-hydroxy-6-methyluracil with ascorbic acid, comparable to the drug “Heptor” (possibly superior).

作者简介

Elvira Repina

Ufa research institute of occupational health and human ecology

编辑信件的主要联系方式.
Email: e.f.repina@bk.ru
ORCID iD: 0000-0001-8798-0846

MD, Ph.D., senior researcher of the department of toxicology and genetics with an experimental clinic of laboratory animals Ufa Research Institute of Occupational Health and Human Ecology, Ufa, 450106, Russia.

e-mail: e.f.repina@bk.ru

俄罗斯联邦

Denis Karimov

Ufa research institute of occupational health and human ecology

Email: noemail@neicon.ru
ORCID iD: 0000-0003-0039-6757
俄罗斯联邦

Samat Baygildin

Ufa research institute of occupational health and human ecology

Email: noemail@neicon.ru
ORCID iD: 0000-0002-1856-3173
俄罗斯联邦

Gulnara Timasheva

Ufa research institute of occupational health and human ecology

Email: noemail@neicon.ru
ORCID iD: 0000-0003-2435-6936
俄罗斯联邦

Nadezhda Khusnutdinova

Ufa research institute of occupational health and human ecology

Email: noemail@neicon.ru
ORCID iD: 0000-0001-5596-8180
俄罗斯联邦

Alfiya Gimadieva

Ufa Institute of Chemistry Ufa Federal Research Center of RAS

Email: noemail@neicon.ru
ORCID iD: 0000-0002-2995-310X
俄罗斯联邦

Lyalya Musina

All-Russian Center for Eye and Plastic Surgery

Email: noemail@neicon.ru
ORCID iD: 0000-0003-1237-9284
俄罗斯联邦

Denis Smolyankin

Ufa research institute of occupational health and human ecology

Email: noemail@neicon.ru
ORCID iD: 0000-0002-7957-2399
俄罗斯联邦

参考

  1. Liss G., Lewis J.H. Drug-induced liver injury: what was new in 2008? Expert Opin. Drug Metab. Toxicol. 2009; 5(8): 843–60. https://doi.org/10.1517/17425250903018904
  2. Morita M., Akai S., Hosomi H., Tsuneyama K., Nakajima M., Yokoi T. Drug-induced hepato-toxicity test using gamma-glutamylcysteine synthetase knockdown rat. Toxicol. Lett. 2009; 189(2): 159–65. https://doi.org/10.1016/j.toxlet.2009.05.016
  3. Vyshtakalyuk A.B., Semenov V.E., Zobov V.V., Galyametdinova I.V., Gumarova L.F., Parfenov A.A., et al. Synthesis and primary evaluation of the hepatoprotective properties of novel pyrimidine derivatives. Bioorganicheskaya khimiya. 2017; 43(5): 572–80. https://doi.org/10.7868/S0132342317040170 (in Russian)
  4. Blyuger A.F. Secrets and Paradoxes of the Liver (ABC of Hepatology) [Tayny i paradoksy pecheni (Azbuka gepatologii)]. Moscow: Znanie; 1988. (in Russian)
  5. Myshkin V.A., Bakirov A.B., Repina E.F. Correction of Lipid Peroxidation is Damaged (Hepatotropic Poisons, Hypoxia, Stress) [Korrektsiya perekisnogo okisleniya lipidov pri povrezhdayushchikh vozdeystviyakh (gepatotropnye yady, gipoksiya, stress)]. Ufa; 2012. (in Russian)
  6. Vengerovskiy A.I., Baturina N.O., Chuchalin V.S., Saratikov A.S. The role of lipid peroxidation in the mechanism of proliferation of fibrous liver tissue in experimental chronic hepatitis. Patologicheskaya fiziologiya i eksperimental’naya terapiya. 1996; (2): 37–9. (in Russian)
  7. Saratikov A.S., Vengerovskiy A.I. Effects of phospholipid-containing hepatoprotectors on cytochrome p-450-dependent antitoxic function of the liver during experimental toxic hepatitis. Byulleten’ eksperimental’noy biologii i meditsiny. 1999; 127(4): 392–4. (in Russian)
  8. Shilova I.V., Krasnov E.A., Suslov N.I. Hepatoprotective properties of fractions from meadowsweet extract during experimental toxic hepatitis. Byulleten’ eksperimental’noy biologii i meditsiny. 2008; 146(7): 54–7. (in Russian)
  9. Bueverov A.O. Oxidative stress and its role in liver damage. Rossiyskiy zhurnal gastroenterologii, gepatologii, koloproktologii. 2002; (4): 21–5. (in Russian)
  10. Skrovtsov V.V. Lipid peroxidation and antioxidant system in hepatology. Gepatologiya. 2003; (3): 7–13. (in Russian)
  11. Cichoż-Lach H., Michalak A. Oxidative stress as a crucial factor in liver diseases. World J. Gastroenterol. 2014; 20(25): 8082–91. https://doi.org/10.3748/wjg.v20.i25.8082
  12. Singal A.K., Jampana S.C., Weinman S.A. Antioxidants as therapeutic agents for liver disease. Liver Int. 2011; 31(10): 1432–48. https://doi.org/10.1111/j.1478-3231.2011.02604.x
  13. Voronina T.A, Smirnov L.D., Dyumaev K.M. Actual directions of use of Mexidol. In: Proceedings of the National Scientific and Practical Conference «Free Radicals, Antioxidants and Human Diseases» [Sbornik trudov natsional’noy nauchno-prakticheskoy konferentsii «Svobodnye radikaly, antioksidanty i bolezni cheloveka»]. Smolensk; 2001: 191–2. (in Russian)
  14. Myshkin V.A., Enikeev D.A. Overcoming Hepatotoxicity with Antioxidants: Reality and Perspective [Preodolenie gepatotoksichnosti antioksidantami: real’nost’ i perspektiva]. Ufa: Poligrafdizayn; 2014. (in Russian)
  15. Myshkin V.A., Bakirov A.B., Repina E.F., Karimov D.O. Experimental Pharmacological Correction of Toxic Liver Damage by Antioxidants [Eksperimental’naya farmakokorrektsiya toksicheskikh porazheniy pecheni antioksidantami]. Ufa: Print-2; 2016. (in Russian)
  16. Li J., Li R.J., Lv G.Y., Liu H.Q. The mechanisms and strategies to protect from hepatic ischemia-reperfusion injury. Eur. Rev. Med. Pharmacol. Sci. 2015; 19(11): 2036–47.
  17. Bilenko M.V. Ischemic and Reperfusion Injuries of Organs (Molecular Mechanisms, Ways of Prevention and Treatment) [Ishemicheskie i reperfuzionnye povrezhdeniya organov (molekulyarnye mekhanizmy, puti preduprezhdeniya i lecheniya)]. Moscow: Meditsina; 1989. (in Russian)
  18. Okovityy S.V., Smirnov A.V. Antihypoxants. Eksperimental’naya i klinicheskaya farmakologiya. 2001; 64(3): 76–80. (in Russian)
  19. Luk’yanova L.D. Modern problems of hypoxia. Vestnik Rossiyskoy Akademii meditsinskikh nauk. 2000; (9): 3–12. (in Russian)
  20. Luk’yanova L.D. Pharmacological correction of mitochondrial dysfunction during hypoxia. In: Ushakov I.B., Luk’yanova L.D., eds. Hypoxia Problems: Molecular, Physiological and Medical Aspects [Problemy gipoksii: molekulyarnye, fiziologicheskie i meditsinskie aspekty]. Moscow: Istoki; 2004: 456–87. (in Russian)
  21. Myshkin V.A., Savlukov A.I., Srubilin D.V., Repina E.F., Yakhina M.R., Kuznetsov I.E. Binary approach to pharmacological correction of oxidative stress in acute hypoxia modeled by sodium nitrite. In: Topical Issues of Occupational Pathology, Hygiene and Human Ecology. Materials of the XLV Scientific-Practical Conference with International Participation «Topical Issues of Modern Occupational Pathology» [Aktual’nye voprosy profpatologii, gigieny i ekologii cheloveka. Materialy XLV nauchno-prakticheskoy konferentsii s mezhdunarodnym uchastiem i seminara «Aktual’nye voprosy sovremennoy profpatologii»]. Kemerovo: Primula; 2010: 137–9. (in Russian)
  22. Skakun N.P. Liver Damage with Carbon Tetrachloride [Porazhenie pecheni chetyrekhkhloristym uglerodom]. Moscow; 1989. (in Russian)
  23. Skakun N.P., Moseychuk I.P., Gil’ L.L. The effectiveness of antioxidants in combined liver damage with carbon tetrachloride and ethanol. Farmakologiya i toksikologiya. 1987; 50(3): 97–9. (in Russian)
  24. Saratikov A.S., Vengerovskiy A.I. New natural hepatoprotective agents. Eksperimental’naya i klinicheskaya farmakologiya. 1995; 58(1): 8–11. (in Russian)
  25. Myshkin V.A., Enikeev D.A. Oxymethyluracil and experimental pathology of the liver. Meditsinskiy vestnik Bashkortostana. 2009; 4(2): 147–51. (in Russian)
  26. Myshkin V.A., Bakirov A.B., Repina E.F., Gimadieva A.R. Hepatoprotection with Oxymethyluracil: Informational and Methodological Letter [Gepatoprotektsiya s primeneniem oksimetiluratsila: Informatsionno-metodicheskoe pis’mo]. Ufa; 2013. (in Russian)
  27. Repina E.F., Myshkin V.A., Karimov D.O., Khusnutdinova N.Yu., Kutlina T.G., Baygil’din S.S., et al. Comparative hepatoprotective efficiency of oximethyluracyl and bemythyl in hepatotoxicity. Meditsina truda i ekologiya cheloveka. 2019; (1): 78–81. https://doi.org/10.24411/2411-3794-2019-10013 (in Russian)
  28. Kozhoka T.G. Medicines in Pharmacotherapy of Cell Pathology. Problems of Production and Provision of the Population [Lekarstvennye sredstva v farmakoterapii patologii kletki. Problemy proizvodstva i obespecheniya naseleniya]. Moscow; 2007. (in Russian)
  29. Mikhaylov I.B. Clinical Pharmacology – the Basics of Rational Pharmacotherapy [Klinicheskaya farmakologiya – osnovy ratsional’noy farmakoterapii]. St. Petersburg: Foliant; 2013. (in Russian)
  30. Repina E.F., Myshkin V.A., Karimov D.O., Timasheva G.V., Khusnutdinova N.Yu., Smolyankin D.A., et al. Antihypoxic activity of the complex compound of oxymethyluracil with ascorbic acid. Toksikologicheskiy vestnik. 2018; (4): 20–3. https://doi.org/10.36946/0869-7922-2018-4-20-23 (in Russian)
  31. Myshkin V.A., Gimadieva A.R., Repina E.F., Karimov D.O., Mustafin A.G., Abdrakhmanov I.B., et al. Complex compound of 5-hydroxy-6-methyluracil with ascorbic acid, exhibiting antihypoxic activity, and a method for its preparation. Patent RF № 2612517; 2017. (in Russian)
  32. Gonskiy Ya.I., Korda M.M., Klits I.N. The effect of acetylcysteine on the antioxidant system in experimental toxic liver damage. Farmakologiya i toksikologiya. 1991; 54(5): 44–6. (in Russian)
  33. Merkulov G.A. Course of Histopathological Technique [Kurs patogistologicheskoy tekhniki]. Moscow: Meditsina; 1969. (in Russian)

补充文件

附件文件
动作
1. JATS XML
下载

版权所有 © Repina E.F., Karimov D.O., Baygildin S.S., Timasheva G.V., Khusnutdinova N.Y., Gimadieva A.R., Musina L.A., Smolyankin D.A., 2024


СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 37884 от 02.10.2009.