Evaluation of the effectiveness of the use of hepatoprotector in acute liver damage by various toxicants in the experiment

Cover Page

Cite item

Full Text

Abstract

Introduction. Acute liver damage with ethanol and its surrogates and chemicals remains an urgent problem. Therefore, studies of the use of hepatoprotector in acute liver damage by various toxicants in the experiment are relevant.

The purpose of this study is an experimental evaluation of the use of ademetionine in the early stages of the toxic effects of carbon tetrachloride and ethanol.

Materials and methods. The therapeutic effect of the drug “Heptor” in acute intoxication with carbon tetrachloride (subcutaneous administration at a dose of 2 g/kg) and ethanol (oral administration at a dose of 4 g/kg weight) was studied. Studies of metabolic processes in the liver were carried out based on biochemical parameters of rat blood serum.

Results. The studies showed that normalization of metabolic processes was observed after introducing “Heptor” against the background of exposure to both toxicants. The therapeutic effect of ademetionine in the case of carbon tetrachloride intoxication had a positive impact after 24 hours of administration and persisted after 72 hours of the experiment. These provisions were based on the results obtained: the restoration of the activity of marker enzymes of hepatocytes (AsAT, AlAT, LDH), the concentration of uric acid and cholesterol, and the indicators of protein metabolism were revealed. The introduction of ademetionine after ethanol intoxication helped restore the function of hepatocytes, which led to the normalization of protein metabolism. The drug stopped hyperenzymemia, which confirmed its membrane-protective properties.

Conclusion. “Heptor” has a regenerating, detoxifying and membrane-protective effect in acute liver lesions with carbon tetrachloride and ethanol. The obtained data confirm the universality of this drug, based on the possibility of using various mechanisms of therapeutic action, which allows us to recommend ademetionine as a hepatoprotector to prevent early liver damage when exposed to high doses of multiple toxicants.

Contribution:
Timasheva G.V. — concept and design of the study, collection and processing of material, statistical processing, writing text, editing;
Bakirov A.B. — concept and design of the study, editing;
Mukhammadieva G.F. — collection of literature data, editing;
Smolyankin D.A., Khusnutdinova N.Yu., Karimov D.D. — collection and processing of the material.
All authors are responsible for the integrity of all parts of the manuscript and approval of the manuscript final version.

Conclusion of the bioethical commission: the study was approved by the bioethical commission of the Ufa Research Institute of Occupational Medicine and Human Ecology, carried out according to the European Convention for the Protection of Vertebrate Animals Used for Experiments or Other Scientific Purposes (ETS N 123), the directive of the European Parliament and the Council of the European Union 2010/63/EU of 22.09.2010 on the protection of animals used for scientific purposes.

Conflict of interest. The authors declare no conflict of interest.

Acknowledgement. The work was carried out within the framework of the industry research program of Federal Service for Supervision in Protection of the Rights of Consumer and Man Wellbeing (Rospotrebnadzor) “Hygienic scientific justification for minimizing risks to the health of the population of Russia” for 2016-2020 on the topic 3.5 Reg. N R & D AAAA16-116022610045-4 Reg. N ICRBS.

Received: May 25, 2021 / Accepted: September 28, 2021 / Published: November 30, 2021

About the authors

Gulnara V. Timasheva

Ufa Research Institute of Occupational Health and Human Ecology

Author for correspondence.
Email: gulnara-vt60@yandex.ru
ORCID iD: 0000-0003-2435-6936

MD, PhD, 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.

e-mail: gulnara-vt60@yandex.ru

Russian Federation

Ahat B. Bakirov

Ufa Research Institute of Occupational Health and Human Ecology; Bashkirian State Medical University

Email: noemail@neicon.ru
ORCID iD: 0000-0003-3510-2595
Russian Federation

Guzel F. Mukhammadieva

Ufa Research Institute of Occupational Health and Human Ecology

Email: noemail@neicon.ru
ORCID iD: 0000-0002-7456-4787
Russian Federation

Denis A. Smolyankin

Ufa Research Institute of Occupational Health and Human Ecology

Email: noemail@neicon.ru
ORCID iD: 0000-0002-7957-2399
Russian Federation

Nadezhda Yu. Khusnutdinova

Ufa Research Institute of Occupational Health and Human Ecology

Email: noemail@neicon.ru
ORCID iD: 0000-0001-5596-8180
Russian Federation

Denis D. Karimov

Ufa Research Institute of Occupational Health and Human Ecology

Email: noemail@neicon.ru
ORCID iD: 0000-0002-1962-2323
Russian Federation

References

  1. State Report «On the state of sanitary and epidemiological welfare of the population in the Russian Federation in 2019». Moscow; 2020. (in Russian)
  2. Konoplya A.I., Loktionov A.L., Dudka V.V., Dolgareva S.A. Chronic intoxication with ethanol: metabolic changes, correction of disturbances. Toksikologicheskiy vestnik. 2015; (5): 25–30. (in Russian)
  3. Roslyy I.M., Abramov C.B., Agaronov V.R., Ivanov A.B., Shulyak Yu.A. Biochemistry and alcoholism (I): metabolic processes in alcoholism. Voprosy narkologii. 2004; (2): 70–7. (in Russian)
  4. Jung Y.C., Namkoong K. Alcohol: intoxication and poisoning – diagnosis and treatment. Handb. Clin. Neurol. 2014; 125: 115–21. https://doi.org/10.1016/b978-0-444-62619-6.00007-0
  5. Chen X., Ying X., Sun W., Zhu H., Jiang X., Chen B. The therapeutic effect of fraxetin on ethanol-induced hepatic fibrosis by enhancing ethanol metabolism, inhibiting oxidative stress and modulating inflammatory mediators in rats. Int. Immunopharmacol. 2018; 56: 98–104. https://doi.org/10.1016/j.intimp.2018.01.027
  6. Klimovich V.V., Maslovskaya A.A., Kuznetsov O.I., Bulat A.V. Characteristics of metabolic state of the rat liver in chronic alcohol intoxication and the use of hepatoprotective mixtures. Zhurnal Grodnenskogo gosudarstvennogo meditsinskogo universiteta. 2007; 18(2): 23–4. (in Russian)
  7. Golofeevskiy V.Yu., Antushevich A.E., Antonov V.G., Grebenyuk A.A. New model of the experimental cirrhosis for estimation hepatoprotective and antifibrotic efficiency of drugs. Eksperimental’naya i klinicheskaya gastroenterologiya. 2017; 146(10): 88–95. (in Russian)
  8. Myshkin V.A., Bakirov A.B., Repina E.F., Karimov D.O. Experimental Pharmacocorrection of Toxic Liver Damage with Antioxidants [Eksperimental’naya farmakokorrektsiya toksicheskikh porazheniy pecheni antioksidantami]. Ufa: Print-2; 2016. (in Russian)
  9. Bakirov A.B., Myshkin V.A., Repina E.F. Pathogenesis and Experimental Correction of Oxidative and Destructive Manifestations of Oxidative Stress [Patogenez i eksperimental’naya korrektsiya okislitel’nykh i destruktivnykh proyavleniy okislitel’nogo stressa]. Ufa; 2015. (in Russian)
  10. Myshkin V.A., Bakirov A.B., Repina Eh.F. Correction of Lipid Peroxidation in Case of Damaging Effects (Hepatotropic Poisons, Hypoxia, Stress) [Korrektsiya perekisnogo okisleniya lipidov pri povrezhdayushchikh vozdeystviyakh (gepatotropnye yady, gipoksiya, stress)]. Ufa: Mir pechati; 2012. (in Russian)
  11. Bueverov A.O. Oxidative stress and its role in liver damage. Gastroenterologiya, gepatologiya, koloproktologiya. 2002; (4): 21–5. (in Russian)
  12. Yang C., Li L., Ma Z., Zhong Y., Pang W., Xiong M. Hepatoprotective effect of methyl ferulic acid against carbon tetrachloride-induced acute liver injury in rats. Exp. Ther. Med. 2018; 15(3): 2228–38. https://doi.org/10.3892/etm.2017.5678
  13. 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
  14. Dai Y., Cederbaum A.I. Cytotoxicity of acetaminophen in human cytochrome P4502E1-transfected HepG2 cells. J. Pharmacol. Exp. Ther. 1995; 273: 1497–505.
  15. Singal A.K., Jampana S.C., Weinman S.A. Antioxidants as therapeutic agents for liver disease. Liver Inter. 2011; 31(10): 1432–48. https://doi.org/10.1111/j.1478-3231.2011.02604.x
  16. Zhang F., Gu J.X., Zou X.P., Zhuge Y.Z. Protective effects of S-adenosylmethionine against CCl4 - and ethanol-induced experimental hepatic fibrosis. Mol. Biol. (Mosk). 2016; 50(2): 284–90. https://doi.org/10.7868/s0026898416020270
  17. Fernandez-Checa J.C., Colell A., Garcia-Ruiz C. S-Adenosyl-L-methionine and mitochondrial reduced glutathione depletion in alcoholic liver disease. Alcohol. 2002; 27(3): 179–83. https://doi.org/10.1016/s0741-8329(02)00229-x
  18. Joseph J.A., Shukitt-Hale B., McEwen J., Rabin B. Magnesium activation of GTP hydrolysis or incubation in S-adenosyl-l-methionine reverses iron-56-particle-induced decrements in oxotremorine enhancement of K+-evoked striatal release of dopamine. Radiat. Res. 1999; 152: 637–41.
  19. Council of Europe. European convention for the protection of vertebrate animals used for experimental and other scientific purpose. Strasbourg; 1986.
  20. Timasheva G.V., Repina E.F., Karimov D.O., Smolyankin D.A., Khusnutdinova N.Yu., Baygil’din S.S. Experimental evaluation of the effectiveness of the use of oxymethyluracil in acute toxic liver damage. Meditsina truda i ekologiya cheloveka. 2020; (4): 79–86. (in Russian)
  21. Kamyshnikov V.S. Handbook of clinical and biochemical research and laboratory diagnostics [Spravochnik po kliniko-biokhimicheskim issledovaniyam i laboratornoy diagnostike]. Moscow: Medpress-inform; 2009. (in Russian)

Supplementary files

Supplementary Files
Action
1. JATS XML

Copyright (c) 2024 Timasheva G.V., Bakirov A.B., Mukhammadieva G.F., Smolyankin D.A., Khusnutdinova N.Y., Karimov D.D.



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.