Morphological changes in the liver of experimental animals in the early stages after correction of exposure to high doses of paracetamol

Мұқаба

Дәйексөз келтіру

Толық мәтін

Аннотация

Introduction. Acetaminophen exhibits hepatotoxicity in overdose, which is the leading cause of drug-induced liver failure. The aim of the research was to study early morphological changes in the liver of experimental animals under the influence of high doses of paracetamol and after correction with hepatoprotectors.

Materials and methods. The corrective effect of various drugs — ademetionine, ethylmethylhydroxypyridine succinate and oxymethyluracil after exposure to high doses of acetaminophen was studied. Acetaminophen was administered to experimental rats once intragastrically at a dose of 1 g/kg, animals received hepatoprotectors twice (after 1 and 24 hours) or four times (after 1, 24, 48, 72 hours) after the toxicant. Morphological studies of the liver of experimental animals were carried out.

Results. Pathomorphological changes were revealed on rat liver preparations after exposure to paracetamol, the most pronounced after 72 hours of exposure. Oxymethyluracil has a protective effect on the structure of the liver during acute exposure to high doses of paracetamol, comparable to the well-known drugs “Heptor” and “Mexidol”. In addition, the protective effect of oxymethyluracil appears earlier.

Limitations. Morphological studies of the liver of 90 white male rats were carried out for studying the corrective action of hepatoprotectors after acute exposure to high doses of acetaminophen and after double (after 1 and 24 hours) or quadruple (after 1, 24, 48, 72 hours) administration of ademethionine, ethylmethylhydroxypyridine succinate and oxymethyluracil, which allowed to determine an effective means to reduce the toxic effect of paracetamol on the liver.

Conclusion. The data obtained may have a certain practical value in terms of the prospective use of oxymethyluracil as an additional effective agent for reducing the toxic effect of paracetamol.

Авторлар туралы

G. Timasheva

«Ufa research institute of occupational health and human ecology»

Хат алмасуға жауапты Автор.
Email: gulnara-vt60@yandex.ru

Candidate of Biological Sciences, Leading Researcher of the Department of Toxicology and Genetics with an experimental clinic of laboratory animals Ufa Research Institute of Occupational Health and Human Ecology, 450106, Ufa, Russian Federation.

e-mail: gulnara-vt60@yandex.ru 

Ресей

Samat Baygildin

«Ufa research institute of occupational health and human ecology»

Email: baigildin.samat@yandex.ru

Младший научный сотрудник отдела токсикологии и генетики с экспериментальной клиникой лабораторных животных ФБУН «Уфимский НИИ медицины труда и экологии человека», 450106, Уфа.

e-mail: baigildin.samat@yandex.ru

Ресей

Ahat Bakirov

«Ufa research institute of occupational health and human ecology»; Bashkirian State Medical University of the Russian Health Ministry

Email: bakirov@anrb.ru

Доктор медицинских наук, профессор, директор ФБУН «Уфимский НИИ медицины труда и экологии человека», 450106, Уфа, заведующий кафедрой терапии и профессиональных болезней с курсом ИДПО БГМУ, 450008, Уфа.

e-mail: bakirov@anrb.ru 

Ресей

Elvira Repina

«Ufa research institute of occupational health and human ecology»

Email: e.f.repina@bk.ru

Кандидат медицинских наук, старший научный сотрудник отдела токсикологии и генетики с экспериментальной клиникой лабораторных животных ФБУН «Уфимский НИИ медицины труда и экологии человека», 450106, Уфа.

e-mail: e.f.repina@bk.ru 

Ресей

Denis Karimov

«Ufa research institute of occupational health and human ecology»

Email: karimovdo@gmail.com

Кандидат медицинских наук, заведующий отделом токсикологии и генетики с экспериментальной клиникой лабораторных животных ФБУН «Уфимский НИИ медицины труда и экологии человека», 450106, Уфа.

e-mail: karimovdo@gmail.com

Ресей

Nadezhda Khusnutdinova

«Ufa research institute of occupational health and human ecology»

Email: h-n-yu@yandex.ru

Научный сотрудник отдела токсикологии и генетики с экспериментальной клиникой лабораторных животных ФБУН «Уфимский НИИ медицины труда и экологии человека», 450106, Уфа.

e-mail: h-n-yu@yandex.ru 

Ресей

Guzel Mukhammadieva

«Ufa research institute of occupational health and human ecology»

Email: ufniimt@mail.ru

Кандидат биологических наук, старший научный сотрудник отдела токсикологии и генетики с экспериментальной клиникой лабораторных животных ФБУН «Уфимский НИИ медицины труда и экологии человека», 450106, Уфа.

e-mail: ufniimt@mail.ru 

Ресей

Әдебиет тізімі

  1. Rumack B.H. Acetaminophen misconceptions. Hepatology. 2004; 40 (1): 10–5.
  2. Ramenskaya G.V., Pilipovich A.A. Combined drug in the treatment of pain syndrome. Nevrologiya. 2017; 20(4): 1006-13. (in Russian)
  3. Marta J.-B., Jerzy Z. Nowak. Paracetamol: Mechanism of Action, Applications and Safety Concern. Environ. Sci. Pollut. 2018; 25(22): 21498-524.
  4. Hazai E., Monostory K., Bakos A., Zacher G., Vereczkey L. About Paracetamol Again. Orv. Hetil. 2001; 142(7): 345-90.
  5. Larson A.M. Acetaminophen hepatotoxicity. Clin. Liver Dis. 2007; 11: 525-48.
  6. Lee W.M. Acetaminophen and the U.S. Acute Liver Failure Study Group: lowering the risks of hepatic failure. Hepatology. 2004; 40(1): 6-9.
  7. Chen C., Hennig G.E., Manautou J.E. Hepatobiliary excretion of acetaminophen glutathione conjugate and its derivatives in transport-deficient (TR-) hyperbilirubinemic rats. Drug Metab. Dispos. 2003; 31(6): 798-804.
  8. Brune K., Renner B., Tiegs G. Acetaminophen/paracetamol: A History of Errors, Failures and False Decisions. Eur. J. Pain. 2015; 19(7): 953-65.
  9. Еремина Е.Ю. Лекарственные поражения печени. Практическая медицина. 2014; 77(1): 20-9.
  10. Bunchorntavakul С., Reddy K.R. Acetaminophen (APAP or N-Acetyl-p-Aminophenol) and Acute Liver Failure. Clin. Liver Dis. 2018; 22(2): 325-46.
  11. Bunchorntavaku C., Reddy K.R. Acetaminophen-related Hepatotoxicity. Clin. Liver Dis. 2013; 17(4): 587-607.
  12. Wang K. Molecular mechanisms of liver injury: apoptosis or necrosis. Exp. Toxicol. Pathol. 2014; 66(8): 351-6.
  13. Liu W.-X., Jia F.-L., He Y.-Y., Zhang B.-X. Protective effects of 5-methoxypsoralen against acetaminophen-induced hepatotoxicity in mice. World J. Gastroenterol. 2012; 18(18): 2197-202.
  14. Zhang J.Y., Song S.D., Pang Q., Zhang R.Y., Wan Y., Yuan D.W., Wu Q.F., Liu C. Hydrogen-rich water protects against acetaminophen-induced hepatotoxicity in mice. World J. Gastroenterol. 2015; 21(14): 4195-209.
  15. Li G., Chen J.-B., Wang Ch., Xu Zh., Nie H., Qin X.-Y., Chen X.-M., Gong Q. Curcumin protects against acetaminophen-induced apoptosis in hepatic injury. World J. Gastroenterol. 2013; 19(42): 7440-6.
  16. Wallace C.I., Dargan P.I., Jones A. L. Paracetamol overdose: an evidence based flowchart to guide management. Emerg. Med. J. 2002; 19(3): 202–5.
  17. Singal A.K., Jampana S.C., Weinman S.A. Antioxidants as therapeutic agents for liver disease. Liver Int. 2011; 31(10): 1432–48.
  18. Katikova O.Yu. The effect of Mexidol on homeostasis and lipid peroxidation during paracetamol intoxication. Eksperimental’naya i klinicheskaya farmakologiya. 2002; 65(6): 53-6. (in Russian)
  19. Xu X.-Y., Hu J.-N., Liu Z., Zhang R., He Y.-F., Hou W., Wang Z.-Q., Yang G., Li W. Saponins (Ginsenosides) From the Leaves of Panax Quinquefolius Ameliorated Acetaminophen-Induced Hepatotoxicity in Mice. Agric Food Chem. 2017; 12: 85-8.
  20. Sandeep B. Subramanya, Balaji Venkataraman, Mohamed Fizur Nagoor Meeran, Sameer N. Goyal, Chandragouda R. Patil, Shreesh Ojha. Therapeutic Potential of Plants and Plant Derived Phytochemicals Against Acetaminophen-Induced Liver Injury. Intern. J. Of Molecul. Science. 2018; 19(12): 3776.
  21. Myshkin V.A., Bakirov A.B. Oxymethyluracil. Ufa: DAR; 2001. (in Russian)
  22. Myshkin V.A., Enikeev D.A., Trubilin D.A., Gimadieva A.R. Experimental evaluation of pyrimidine derivatives on models of liver toxicity: a review. Nauchnoe obozrenie. Medicinskie nauki. 2016; 03: 88-98. (in Russian)
  23. Repina E.F., Gimadieva A.R., Myshkin V.A., Bakirov A.B., Timasheva G.V., Husnutdinova N.Yu. et al. Antihypoxic activity of a new complex compound of oxymethyluracil with sodium succinate. Toksikologicheskij vestnik. 2017; 2: 40-42. (in Russian)
  24. Repina E.F., Myshkin V.A., Karimov D.O., Timasheva G.V., Husnutdinova N.Yu., Smolyankin D.A. et al. Antihypoxic activity of the complex compound of oxymethyluracil with ascorbic acid. Toksikologicheskij vestnik. 2018; 4: 20-24. (in Russian)
  25. Repina E.F., Karimov D.O., Timasheva G.V., Husnutdinova N.Yu., Gimadieva A.R., Musina L.A., Muhammadieva G.F., Bajgildin S.S. Experimental evaluation of the hepatoprotective activity of a new composition of oxymethyluracil with carboxylic acids. Gigiena i sanitariya. 2019; 9: 1004-1011. (in Russian)
  26. Timasheva G.V., Karimov D.O., Repina E.F., Smolyankin D.A., Husnutdinova N.Yu., Muhammadieva G.F., Bajgildin S.S. Metabolic changes during acute exposure to paracetamol and assessment of the effectiveness of hepatoprotective drugs. Gigiena i sanitariya. 2020; 99 (9): 1016-1021. (in Russian)
  27. Yakupova T.G., Muhammadieva G.F., Karimov D.O., Kutlina E.G., Bakirov A.B., Valova Yа.V., Bajgildin S.S., Ziatdinova M.M. Transcriptional activity of genes of the glutathione system in toxic hepatitis caused by paracetamol. Eksperimental’naya i klinicheskaya gastroenterologiya. 2020; 176(4): 121-127. (in Russian)

Қосымша файлдар

Қосымша файлдар
Әрекет
1. JATS XML
Жүктеу

© Timasheva G.V., Baygildin S.S., Bakirov A.B., Repina E.F., Karimov D.O., Khusnutdinova N.Y., Mukhammadieva G.F., 2022


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 - 81728 от 11 декабря 2013.