EFFECT OF 2-ETHYL-6-METHYL-3-HYDROXYPYRIDINE DERIVATIVE ON THE COURSE OF NONALCOHOLIC FATTY LIVER DISEASE IN THE EXPERIMENT

DOI: https://doi.org/10.29296/24999490-2020-01-04

D.S. Sukhanov(1), D.Yu. Ivkin(1), G.A. Plisko(1), A.V. Karavaeva(1), M.V. Krasnova(1), M.A. Poveryaeva(1), V.E. Karev(2), A.V. Bunyat(1), I.L. Stepanova(1), S.V. Okovityj(1), 1-St. Petersburg State Chemical Pharmaceutical University, Professor Popov str., 14, Lit. A, St. Petersburg, 197022, Russian Federation; 2F-ederal Medical and Biological Agency Federal State Institution Scientic and Researh Institute of Children’s Infections, Professor Popov str., 9, St. Petersburg, 197022, Russian Federation Е-mail: [email protected]

Introduction. In the treatment of non-alcoholic fatty liver disease (NAFLD), which is the main cause of chronic liver disease, a certain role is assigned to hepatoprotectors. One of the hepatoprotectors currently used to treat NAFLD is ademetionine. At the same time, a number of preclinical and clinical studies have shown hepatotropic activity of 2-ethyl-6-methyl-3-hydroxypyridine succinate (EMHPS) both in hypodynamic conditions and in NAFLD. The aim of the study. Comparative evaluation of the effectiveness of the new compound-2-ethyl-6-methyl-3-sulfopyridine (EMSP), a derivative of 2-ethyl-6-methyl-3-hydroxypyridine, in comparison with 2-ethyl-6-methyl-3-hydroxypyridine succinate (Armadin) and ademetionine (Heparetta) on the model of experimental nonalcoholic fatty liver disease. Methods. The study was conducted on 125 inbred male mice of the C57BL/6 line, weighing 18–20 g. by randomization, the animals were divided into 5 groups (n=25 in each): intact animals, control without treatment, group 3-NAFLD + EMSP model, 4-NAFLD + EMGPS model, 5-NAFLD + ademetionin model. NAFLD was modeled by combining a high-fat diet and the administration of a toxicant (carbon tetrachloride). Results. It was established that against the background of the introduction of the studied compound, there was a decrease in animal mortality in combination with a positive effect on the morphological picture of the liver. By the end of the 4th month of the experiment, a decrease in the frequency of necrotic changes and liver fibrosis was observed, while fibrosis of degree F1 in one case of observation was reversible and was not determined by the end of the experiment. The indicated compound has a moderate anticytolytic effect, as well as a hypocholesterolemic effect in the early stages of application. The efficacy of 2-ethyl-6-methyl-3-sulfopyridine and comparison drugs on the NAFLD model used was comparable. Conclusion. Taking into account the positive effect of the studied compound on the survival of animals in combination with the improvement of the histological picture of the liver in NAFLD, comparable with comparison drugs, it is advisable to further study EMSP in the experiment.
Keywords: 
2-ethyl-6-methyl-3-sulfapiridin, 2-ethyl-6-methyl-3-hydroxypyridine succinate, Armadon, ademetionine, Giaretta, non-alcoholic fatty liver disease NAFLD
Список литературы: 
  1. Poluhina A.V., Vinnitskaja E.V,, Sandler Ju.G., Hajmenova T.Ju. Ademetionin v lechenii nealkogol'noj zhirovoj bolezni pecheni. Meditsinskij Sovet. 2015; 15: 104–11. https://doi.org/10.21518/2079-701X-2017-15-104-111. [Poluhina A.V., Vinnickaya E.V., Sandler YU.G., Hajmenova T.YU. Ademetionine in the treatment of nonalcoholic fatty liver disease. Meditsinskiy sovet. 2015; 15: 104–11 (In Russian)]
  2. Katikova O.Ju. Vlijanie meksidola na funktsii i strukturu pecheni, parametry perekisnogo okislenija lipidov pri dlitel'noj gipodinamii. Eksperimental'naja i klinicheskaja farmakologija. 2009; 2: 51–4. https://doi.org/10.30906/0869-2092-2009-72-2-51-54/ [Katikova O.YU. The effect of Mexidol on the function and structure of liver, parameters of lipid peroxidation during long-term inactivity. Eksp. Klin. Farmakol. 2009; 2: 51–4 (In Russian)]
  3. Castro RE, Deihl AM. Towards a definite mouse model of NAFLD. J. Hepatol. 2018; 69 (2): 272–4. https://doi.org/10.1016/j.jhep.2018.05.002/
  4. Ivashkin V.T., Majevskaja M.V., Pavlov Ch.S., Tihonov I.N., Shirokova E.N., Bueverov A.O., Drapkina O.M., Shul'pekova Ju.O., Tsukanov V.V., Mammaev S.N., Maev I.V., Pal'gova L.K. Klinicheskie rekomendatsii po diagnostike i lecheniju nealkogol'noj zhirovoj bolezni pecheni Rossijskogo obschestva po izucheniju pecheni i Rossijskoj gastroenterologicheskoj assotsiatsii. Rossijskij zhurnal gastroenterologii, gepatologii i koloproktologii. 2016; 2: 24–42. https://doi.org/10.22416/1382-4376-2016-26-2-24-42 [Ivashkin V. T., Mayevskaya M. V., Pavlov CH. S., Tikhonov I. N., Shirokova E. N., bueverov A. O., Drapkina O. M., Shulpekova Yu. O., Tsukanov V. V., Mammaev S. N., Mayev I. V., Palgova L. K. Clinical recommendations for the diagnosis and treatment of nonalcoholic fatty liver disease of the Russian society for the study of the liver and the Russian gastroenterological association. Russian Journal of Gastroenterology, Hepatology, Coloproctology. 2016; 2: 24–42 (In Russian)]
  5. Chalasani N., Younossi Z., Lavine J.E., Charlton M., Cusi K., Rinella M., Harrison S.A., Brunt E.M., Sanyal A.J. The diagnosis and management of nonalcoholic fatty liver disease: Practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2018; 67 (1): 328–57. https://doi.org/10.1002/hep.29367