Metabolic changes on the background of acute exposure to paracetamol and evaluation of the effectiveness of hepatoprotective drug

Cover Page

Cite item

Full Text

Abstract

Introduction. In modern conditions, caused by the pandemic of a new type of viral infection Covid 19, the use of paracetamol, which has hepatotoxic properties in overdose, has increased. It seems relevant to study metabolic disorders in the liver in acute paracetamol intoxication and evaluate the effectiveness of the timely use of hepatoprotective drugs.

The purpose of this study is an experimental assessment of metabolic changes at the early stages of paracetamol exposure and pharmacological correction of toxic liver lesions with oxymethyluracil in comparison with known hepatoprotectors – ademetionine and Mexidol.

Material and methods. Acute intragastric administration of paracetamol to laboratory animals was performed, and the corrective effect of the drug oxymethyluracil was studied in comparison with “Heptor” and “Mexidol”. Biochemical studies of biomaterial of laboratory animals were conducted.

Results. The analysis found the use of known hepatoprotectors and oxymethyluracil after exposure to paracetamol to normalize the biochemical parameters that characterize the functional state of the liver in laboratory animals.

Conclusion. Oxymethyluracil, along with known hepatoprotectors, has a protective effect on the liver of laboratory animals under acute exposure to paracetamol comparable to, and in some cases exceeding, the corrective action of “Heptor” and “Mexidol”.

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, Ph.D.. Leading researcher, Department of Toxicology and Genetics with an experimental clinic of laboratory animals Ufa Research Institute of Occupational Health and Human Ecology, Ufa, 450106, Russian Federation.

e-mail: gulnara-vt60@yandex.ru

Russian Federation

D. O. Karimov

Ufa Research Institute of Occupational Health and Human Ecology

Email: noemail@neicon.ru
ORCID iD: 0000-0003-0039-6757
Russian Federation

E. F. Repina

Ufa Research Institute of Occupational Health and Human Ecology

Email: noemail@neicon.ru
ORCID iD: 0000-0001-8798-0846
Russian Federation

D. A. Smolyankin

Ufa Research Institute of Occupational Health and Human Ecology

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

N. Yu. Khusnutdinova

Ufa Research Institute of Occupational Health and Human Ecology

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

G. F. Mukhammadieva

Ufa Research Institute of Occupational Health and Human Ecology

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

S. S. Baygildin

Ufa Research Institute of Occupational Health and Human Ecology

Email: noemail@neicon.ru
ORCID iD: 0000-0002-1856-3173
Russian Federation

References

  1. Ramenskaya G.V., Pilipovich A.A. Combination medication in the therapy of pain syndrome. Russkiy meditsinskiy zhurnal. 2017; 20(4): 1006–13. (in Russian)
  2. Jóźwiak-Bebenista M., Nowak J.Z. Paracetamol: mechanism of action, applications and safety concern. Acta Pol. Pharm. 2014; 71(1): 11–23.
  3. Hazai E., Monostory K., Bakos A., Zacher G., Vereczkey L. About paracetamol again. Orv. Hetil. 2001; 142(7): 345–90. (in Hu)
  4. State register of medicines. Available at: http://grls.rosminzdrav.ru/grls.aspx (in Russian)
  5. Sarrell E.M., Wielunsky E., Cohen H.A. Antipyretic treatment in young children with fever: acetaminophen, ibuprofen, or both alternating in a randomized, double-blind study. Arch. Pediatr. Adolesc. Med. 2006; 160(2): 197–202. https://doi.org/10.1001/archpedi.160.2.197
  6. Hollinghurst S., Redmond N., Costelloe C., Montgomery A., Fletcher M., Peters T.J., et al. Paracetamol plus ibuprofen for the treatment of fever in children (PITCH): economic evaluation of a randomized controlled trial. BMJ. 2008; 337: a1490. https://doi.org/10.1136/bmj.a1490
  7. Tanatarov S.Z. Parenteral administration of paracetamol for improve of anesthesia in surgical oncology. Vestnik Avitsenny. 2012; (2): 84–7. (in Russian)
  8. Kalantzi L., Reppas C., Dressman J.B., Amidon G.L., Junginger H.E., Midha K.K., et al. Biowaiver monographs for immediate release solid oral dosage forms: acetaminophen (paracetamol). J. Pharm. Sci. 2006; 95(1): 4–14. https://doi.org/10.1002/jps.20477
  9. Brune K., Renner B., Tiegs G. Acetaminophen/paracetamol: a history of errors, failures and false decisions. Eur. J. Pain. 2015; 19(7): 953–65. https://doi.org/10.1002/ejp.621
  10. Eremina E.Yu. Drug damage to the liver. Prakticheskaya meditsina. 2014; 77(1): 20–9. (in Russian)
  11. Bunchorntavakul С., Reddy K.R. Acetaminophen (APAP or N-acetyl-p-aminophenol) and acute liver failure. Clin. Liver Dis. 2018; 22(2): 325–46. https://doi.org/10.1016/j.cld.2018.01.007
  12. Bunchorntavaku C., Reddy K.R. Acetaminophen-related hepatotoxicity. Clin. Liver Dis. 2013; 17(4): 587–607. https://doi.org/10.1016/j.cld.2013.07.005
  13. Wang X., Wu Q., Liu A., Anadón A., Rodríguez J.L., Martínez-Larrañaga M.R., et al. Paracetamol: overdose-induced oxidative stress toxicity, metabolism, and protective effects of various compounds in vivo and in vitro. Drug. Metab. Rev. 2017; 49(4): 395–437. https://doi.org/10.1080/03602532.2017.1354014
  14. Xu X.Y., Hu J.N., Liu Z., Zhang R., He Y.F., Hou W., et al. Saponins (ginsenosides) from the leaves of Panax quinquefolius ameliorated acetaminophen-induced hepatotoxicity in mice. J. Agric. Food Chem. 2017; 65(18): 3684–92. https://doi.org/10.1021/acs.jafc.7b00610
  15. Subramanya S.B., Venkataraman B., Meeran M.F.N., Goyal S.N., Patil C.R., Ojha S. Therapeutic potential of plants and plant derived phytochemicals against acetaminophen-induced liver injury. Int. J. Mol. Sci. 2018; 19(12): 3776. https://doi.org/10.3390/ijms19123776
  16. 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)
  17. Zhang F., Gu J.X., Zou X.P., Zhuge Y.Z. Protective effects of S-adenosylmethionine against CCl4 – and ethanol-induced experimental hepatic fibrosis. Molekulyarnaya biologiya. 2016; 50(2): 284–90. https://doi.org/10.7868/S0026898416020270 (in Russian)
  18. Gong Z., Yan S., Zhang P., Huang Y., Wang L. Effects of S-adenosylmethionine on liver methionine metabolism and steatosis with ethanol-induced liver injury in rats. Hepatol. Int. 2008; 2(3): 346–52. https://doi.org/10.1007/s12072-008-9082-1
  19. Katikova O.Yu. The effect of mexidol on the state of homeostasis and lipid peroxidation in guinea pigs intoxicated with paracetamol. Eksperimental’naya i klinicheskaya farmakologiya. 2002; 65(6): 53–6. https://doi.org/10.30906/0869-2092-2002-65-6-53-56 (in Russian)
  20. Myshkin V.A., Bakirov A.B. Oxymethyluracil [Oksimetiluratsil]. Ufa: DAR; 2001. (in Russian)
  21. 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)
  22. Myshkin V.A., Enikeev D.A., Srubilin D.A., Gimadieva A.R. Experimental evaluation of pyrimidine derivatives using models of the toxically damaged liver: a review. Meditsinskie nauki. 2016; (3): 88–98. (in Russian)
  23. 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; 151(4): 20–3. https://doi.org/10.36946/0869-7922-2018-4-20-23 (in Russian)
  24. Kamyshnikov V.S. Handbook of Clinical and Biochemical Research and Laboratory Diagnostics [Spravochnik po kliniko-biokhimicheskim issledovaniyam i laboratornoy diagnostike]. Moscow: Medpress-infom; 2009. (in Russian)
  25. Eremina E.Yu. Drug-induced liver diseases. Prakticheskaya meditsina. 2014; (1): 20–9. (in Russian)
  26. Bibik E.Yu., Krivokolysko B.S., Burdeynaya A.A., Demenko A.V., Frolov K.A., Dotsenko V.V., et al. Effects of partially hydrogenated pyridines (cyanothioacetamide derivatives) on the blood of rats with combined paracetamol-alcoholic liver injury. Kubanskiy nauchnyy meditsinskiy vestnik. 2019; 26(2): 106–14. https://doi.org/10.25207/1608-6228-2019-26-2-106-114. (in Russian)
  27. Mirsaev T.R. Hepatoprotective activity of oxymethyluracil. Farmatsiya. 2007; (2): 34–5. (in Russia)
  28. Vyshkatalyuk A.B., Semenov V.E., Zobov V.V., Galyametdinova I.V., Gumarova L.F., Parfenov A.A. 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)

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2024 Timasheva G.V., Karimov D.O., Repina E.F., Smolyankin D.A., Khusnutdinova N.Y., Mukhammadieva G.F., Baygildin S.S.


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.