vestimИзвестия Национальной академии наук Беларуси. Серия медицинских наукProceedings of the National Academy of Sciences of Belarus, Medical series1814-60232524-2350The Republican Unitary Enterprise Publishing House "Belaruskaya Navuka"10.29235/1814-6023-2019-16-1-56-64vestim-476Research ArticleКЛИНИЧЕСКАЯ И ЭКСПЕРИМЕНТАЛЬНАЯ МЕДИЦИНАCLINICAL AND EXPERIMENTAL MEDICINEГепатопротекторная эффективность самоэмульгирующейся композиции с берберином при экспериментальном токсическом поражении печени ацетаминофеномHepatoprotective action of the self-emulsifying system with berberine in experimental toxic liver injury by acetaminofenСутькоИ. П.SutskoI. P.

Сутько Ирина Петровна – кандидат биологических наук, старший научный сотрудник

бульвар Ленинского комсомола, 50, 230030, г. Гродно

Iryna P. Sutsko – Ph. D. (Biol.), Senior researcher

50, Lenin Komsomol Boulevard, 230030, Grodno

irina_sutsko@list.ruШляхтунА. Г.ShlyahtunA. G.

Шляхтун Алексей Генрихович – научный сотрудник, исполняющий обязанности заведующего отделом

бульвар Ленинского комсомола, 50, 230030, г. Гродно

Alexej G. Shlyahtun – Researcher, Acting Head of the Department

50, Lenin Komsomol Boulevard, 230030, Grodno

a.shlyahtun@gmail.comТиткоО. В.TitkoO. V.

Титко Оксана Викторовна – младший научный сотрудник

бульвар Ленинского комсомола, 50, 230030, г. Гродно

Oksana V. Titko – Junior researcher

50, Lenin Komsomol Boulevard, 230030, Grodno

o.titko@mail.ruЯнкевичН. В.YankevichN. V.

Янкевич Надежда Викторовна – научный сотрудник

бульвар Ленинского комсомола, 50, 230030, г. Гродно

Nadezhda V. Yankevich – Researcher

50, Lenin Komsomol Boulevard, 230030, Grodno

aurika@tut.byТелегинП. Г.TeleginP. G.

Телегин Павел Геннадьевич – младший научный сотрудник

бульвар Ленинского комсомола, 50, 230030, г. Гродно

Pavel G. Telegin – Junior researcher

50, Lenin Komsomol Boulevard, 230030, Grodno

p.telegin@tut.byКолодкоА. В.KolodkoA. V.

Колодко Анастасия Васильевна – младший научный сотрудник

бульвар Ленинского комсомола, 50, 230030, г. Гродно

Anastasia V. Kolodko – Junior researcher

50, Lenin Komsomol Boulevard, 230030, Grodno

askamatyulkoz@mail.ruЗверинскийИ. В.ZverinskyI. V.

Зверинский Игорь Владимирович – кандидат биологических наук, заведующий отделом

бульвар Ленинского комсомола, 50, 230030, г. Гродно

Igor V. Zverinsky – Ph. D. (Biol.), Head of the Department

50, Lenin Komsomol Boulevard, 230030, Grodno

zverinsky@tut.byИнститут биохимии биологически активных соединений НАН БеларусиInstitute of Biochemistry of Biologically Active Compounds of the National Academy of Sciences of Belaru2019120320191615664Copyright © Сутько И.П., Шляхтун А.Г., Титко О.В., Янкевич Н.В., Телегин П.Г., Колодко А.В., Зверинский И.В., 20192019Сутько И.П., Шляхтун А.Г., Титко О.В., Янкевич Н.В., Телегин П.Г., Колодко А.В., Зверинский И.В.Sutsko I.P., Shlyahtun A.G., Titko O.V., Yankevich N.V., Telegin P.G., Kolodko A.V., Zverinsky I.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vestimed.belnauka.by/jour/article/view/476

На модели токсического поражения печени крыс ацетаминофеном изучено гепатопротекторное действие самоэмульгирующейся композиции с берберином и проведен анализ ее гепатозащитных свойств в сравнении с берберином в свободном виде. Показано, что курсовое введение самоэмульгирующейся композиции с берберином до интоксикации крыс ацетаминофеном в большей степени препятствует развитию цитолиза гепатоцитов, а также способствует усилению глутатионового звена антиоксидантной системы, повышая содержание общих и свободных сульфгидрильных групп по сравнению с введением животным берберина в свободном виде.

The hepatoprotective effect of the self-emulsifying composition with berberine was studied in the model of toxic liver damage in rats with acetaminophen and its hepatoprotective properties were analyzed in comparison with the use of berberine in free form. The course introduction of self-emulsifying composition with berberine before intoxication of rats with acetaminophen to a greater extent inhibits the development of cytolysis of hepatocytes, and also promotes the enhancement of the glutathione unit of the antioxidant system, increasing the content of total and free sulfhydryl groups, compared with the introduction of free berberine in animals.

берберинсамоэмульгирующаяся системамикроэмульсииацетаминофенгепатотоксичностьberberineself-emulsifying systemmicroemulsionsacetaminophenhepatotoxicityReferencesThe metabolism of berberine and its contribution to the pharmacological effects / K. Wang [et al.] // Drug Metab. Rev. – 2017. – Vol. 49, N 2. – P. 139–157. https://doi.org/10.1080/03602532.2017.1306544Wang K., Feng X., Chai L., Cao S., Qiu F. The metabolism of berberine and its contribution to the pharmacological effects. Drug Metabolism Reviews, 2017, vol. 49, no. 2, pp. 139–157. https://doi.org/10.1080/03602532.2017.1306544Current knowledge and pharmacological profle of berberine: an update / A. Kumar [et al.] // Eur. J. Pharmacol. – 2015. – Vol. 761. – P. 288–297. https://doi.org/10.1016/j.ejphar.2015.05.068Kumar A., Ekavali E., Chopra K., Mukherjee M., Pottabathini R., Dhull D. K. Current knowledge and pharmacological profle of berberine: An update. European Journal of Pharmacology, 2015, vol. 761, pp. 288–297. https://doi.org/10.1016/j.ejphar.2015.05.068Imanshahidi, M. Berberis vulgaris and berberine: An update review / M. Imanshahidi, H. Hosseinzadeh // Phytother. Res. – 2016. – Vol. 30, N 11. – P. 1745–1764. https://doi.org/10.1002/ptr.5693Imanshahidi M., Hosseinzadeh H. Berberis vulgaris and berberine: An update review. Phytotherapy Research, 2016, vol. 30, no. 11, pp. 1745–1764. https://doi.org/10.1002/ptr.5693Hepatoprotective effects of berberine on liver fbrosis via activation of AMP-activated protein kinase / J. Li [et al.] // Life Sci. – 2014. – Vol. 98, N 1. – P. 24–30. https://doi.org/10.1016/j.lfs.2013.12.211Li J., Pan Y., Kan M., Xiao X., Wang Y., Guan F., Zhang X., Chen L. Hepatoprotective effects of berberine on liver fbrosis via activation of AMP-activated protein kinase. Life Sciences, 2014, vol. 98, no. 1, pp. 24–30. https://doi.org/10.1016/j.lfs.2013.12.211Влияние берберина на функциональное состояние печени крыс после перевязки общего желчного протока / И. В. Зверинский [и др.] // Биомед. химия. – 2013. – Т. 59, № 1. – С. 90–96.Zverinsky I. V., Melnichenko N. G., Poplavsky V. A., Sutsko I. P., Telegin P. G., Shlyahtun A. G. The effect of berberine administration to rats on the functional state of liver after common bile duct ligation. Biochemistry (Moscow) Supplement Series B: Biomedical Chemistry, 2012, vol. 6, no. 2, pp 159–163 https://doi.org/10.1134/S1990750812020163Влияние берберина на восстановление активности ферментов биотрансформации ксенобиотиков печени крыс после частичной гепатэктомии / И. В. Зверинский [и др.] // Биомед. химия. – 2015. – Т. 61, № 3. – С. 381–383.Zverinskii I. V., Zverinskaya N. G., Sut’ko I. P., Telegin P. G., Shlyakhtun A. G. Effects of berberine on the recovery of rat liver xenobiotic-metabolizing enzymes after partial hepatectomy. Biomeditsinskaya khimiya = Biochemistry (Moscow) Supplement Series B: Biomedical Chemistry, 2015, vol. 61, no. 3, pp. 381–383 (in Russian).Research progress on berberine with a special focus on its oral bioavailability / C.-S. Liu [et al.] // Fitoterapia. – 2016. – Vol. 109. – P. 274–282. https://doi.org/10.1016/j.ftote.2016.02.001Liu C.-S., Zheng Y.-R., Zhang Y.-F., Long X.-Y. Research progress on berberine with a special focus on its oral bioavailability. Fitoterapia, 2016, vol. 109, pp. 274–282. https://doi.org/10.1016/j.ftote.2016.02.001Extensive intestinal frst-pass elimination and predominant hepatic distribution of berberine explain its low plasma levels in rats / Y.-T. Liu [et al.] // Drug Metab. Dispos. – 2010. – Vol. 38, N 10. – P. 1779–1784. https://doi.org/10.1124/dmd.110.033936Liu Y.-T., Hao H.-P., Xie H.-G., Lai L., Wang Q., Liu C.-X., Wang G.-J. Extensive intestinal frst-pass elimination and predominant hepatic distribution of berberine explain its low plasma levels in rats. Drug Metabolism and Disposition, 2010, vol. 38, no. 10, pp. 1779–1784. https://doi.org/10.1124/dmd.110.033936Вергун, О. М. Острые отравления парацетамолом, диагностика / О. М. Вергун, С. Н. Борисевич, В. С. Камышников // Лабораторная диагностика. Восточная Европа. – 2015. – № 2 (14). – С. 113–118.Vergun О., Borisevich S., Kamyschnikov V. Acute paracetamol intoxication, diagnostics. Laboratornaya diagnostika. Vostochnaya Evropa = Laboratory diagnostics. Eastern Europe, 2015, no. 2 (14), pp. 113–118 (in Russian).Acetaminophen from liver to brain: New insights into drug pharmacological action and toxicity // C. I. Ghanem [et al.] // Pharmacol. Res. – 2016. – Vol. 109. – P. 119–131. https://doi.org/10.1016/j.phrs.2016.02.020Ghanem C. I., Pérez M. J., Manautou J. E., Mottino A. D. Acetaminophen from liver to brain: New insights into drug pharmacological action and toxicity. Pharmacological Research, 2016, vol. 109, pp. 119–131. https://doi.org/10.1016/j.phrs.2016.02.020Граник, В. Г. Токсикология лекарств / В. Г. Граник. – М. : Вузовская книга, 2009. – 440 с.Granik V. G. Toxicology of drugs. Moscow, Vuzovskaya kniga Publ., 2009. 440 p. (in Russian).Ghosh, P. K. Microemulsions: a potential drug delivery system // P. K. Ghosh, R. S. Murthy // Curr. Drug Deliv. – 2006. – Vol. 3, N 2. – P. 167–180. https://doi.org/10.2174/156720106776359168Ghosh P. K., Murthy R. S. Mic roemulsions: a potential drug delivery system. Current Drug Delivery, 2006, vol. 3, no. 2, pp. 167–180. https://doi.org/10.2174/156720106776359168Gursoy, R. N. Self-emulsifying drug delivery systems (SEDDS) for improved oral delivery of lipophilic drugs / R. N. Gursoy, S. Benita // Biomed. Pharmacother. – 2004. – Vol. 58, N 3. – P. 173–182. https://doi.org/10.1016/j.biopha.2004.02.001Gursoy R. N., Benita S. Self-emulsifying drug delivery systems (SEDDS) for improved oral delivery of lipophilic drugs. Biomedicine and Pharmacotherapy, 2004, vol. 58, no. 3, pp. 173–182. https://doi.org/10.1016/j.biopha.2004.02.001Lipid-based systems as a promising approach for enhancing the bioavailability of poorly water-soluble drugs / K. Cerpnjak [et al.] // Acta Pharm. – 2013. – Vol. 63, N 4. – P. 427–445. https://doi.org/10.2478/acph-2013-0040Cerpnjak K., Zvonar A., Gašperlin M., Vrečer F. Lipid-based systems as a promising approach for enhancing the bioavailability of poorly water-soluble drugs. Acta Pharmaceutica, 2013, vol. 63, no. 4, pp. 427–445. https://doi.org/10.2478/acph-2013-0040Ellman, G. L. Tissue sulfhydryl groups / G. L. Ellman // Arch. Biochem. Biophys. – 1959. – Vol. 82, N 1. – P. 70–71. https://doi.org/10.1016/0003-9861(59)90090-6Ellman G. L. Tissue sulfhydryl groups. Archives of Biochemistry and Biophysics, 1959, vol. 82, no. 1, pp. 70–71. https://doi.org/10.1016/0003-9861(59)90090-6Sedlak, J. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent // J. Sedlak, R. H. Lindsay // Anal. Biochem. – 1968. – Vol. 25. – P. 192–205. https://doi.org/10.1016/0003-2697(68)90092-4Sedlak J., Lindsay R. H. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Analytical Biochemistry, 1968, vol. 25, pp. 192–205. https://doi.org/10.1016/0003-2697(68)90092-4Carlberg, I. Glutathione reductase / I. Carlberg, B. Mannervick // Methods Enzymol. – 1985. – Vol. 113. – P. 484–490. https://doi.org/10.1016/S0076-6879(85)13062-4Carlberg I., Mannervick B. Glutathione reductase. Methods in Enzymology, 1985, vol. 113, pp. 484–490. https://doi.org/10.1016/S0076-6879(85)13062-4Habig, W. J. Glutathione S-transferase, the frst enzymatic step in mercapturic acid formation / W. J. Habig, M. J. Pabst, W. B. Jacoby // J. Biol. Chem. – 1974. – Vol. 249, N 22. – P. 7130–7139.Habig W. J., Pabst M. J., Jacoby W. B. Glutathione S-transferase, the frst enzymatic step in mercapturic acid formation. Journal of Biological Chemistry, 1974, vol. 249, no. 22, pp. 7130–7139.Martinez, J. I. A sensitive fluorimetric microassay for the determination of glutathione peroxidase activity. Application to human blood platelets / J. I. Martinez, J.-M. Launay, C. Dreux // Anal. Biochem. – 1979. – Vol. 98, N 1. – P. 154–159. https://doi.org/10.1016/0003-2697(79)90720-6Martinez J. I., Launay J.-M., Dreux C. A sensitive fluorimetric microassay for the determination of glutathione peroxidase activity. Application to human blood platelets. Analytical Biochemistry, 1979, vol. 98, no. 1, pp. 154–159. https://doi.org/10.1016/0003-2697(79)90720-6Tamura, T. A new selenoprotein from human lung adenocarcinoma cells: purifcation, properties and thioredoxin activity / T. Tamura, T. C. Stadtman // Proc. Natl. Acad. Sci. USA. – 1996. – Vol. 93, N 3. – P. 1006–1011. https://doi.org/10.1073/pnas.93.3.1006Tamura T., Stadtman T. C. A new selenoprotein from human lung adenocarcinoma cells: purifcation, properties and thioredoxin activity. Proceedings of the National Academy of Sciences, 1996, vol. 93, no. 3, pp. 1006–1011. https://doi.org/10.1073/pnas.93.3.1006Balamir, A. NADP-linked isocitrate dehydrogenase from beef liver: a new method of purifcation and the effect of metal ion cofactor on its stability // A. Balamir // Biochem. Med. – 1983. – Vol. 29, N 2. – P. 194–206. https://doi.org/10.1016/0006-2944(83)90040-6Balamir A. NADP-linked isocitrate dehydrogenase from beef liver: a new method of purifcation and the effect of metal ion cofactor on its stability. Biochemical Medicine, 1983, vol. 29, no. 2, pp. 194–206. https://doi.org/10.1016/0006-2944(83)90040-6Glock, G. E. Further studies on the properties and assay of glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase of rat liver / G. E. Glock, P. McLean // Biochem. J. – 1953. – Vol. 55, N 3. – P. 400–408. https://doi.org/10.1042/bj0550400Glock G. E., McLean P. Further studies on the properties and assay of glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase of rat liver. Biochemical Journal, 1953, vol. 55, no. 3, pp. 400–408. https://doi.org/10.1042/bj0550400Protein measurement with the Folin phenol reagent / O. H. Lowry [et al.] // J. Biol. Chem. – 1951. – Vol. 193, N 1. – Р. 265–275.Lowry O. H., Rosebrough N. J., Farr A. L., Randall R. J. Protein measurement with the Folin phenol reagent. Journal of Biological Chemistry, 1951, vol. 193, no. 1, pp. 265–275.Berberine protects liver from ethanol-induced oxidative stress and steatosis in mice / P. Zhang [et al.] // Food Chem. Toxicol. – 2014. – Vol. 74. – P. 225–232. https://doi.org/10.1016/j.fct.2014.10.005Zhang P., Ma D., Wang Y., Zhang M., Qiang X., Liao M., Liu X., Wu H., Zhang Y. Berberine protects liver from ethanol-induced oxidative stress and steatosis in mice. Food and Chemical Toxicology, 2014, vol. 74, pp. 225–232. https://doi.org/10.1016/j.fct.2014.10.005Forrest, J. A. Clinical pharmacokinetics of paracetamol // J. A. Forrest, J. A. Clements, L. F. Prescott // Clin. Pharmacokinet. – 1982. – Vol. 7, N 2. – P. 93–107. https://doi.org/10.2165/00003088-198207020-00001Forrest J. A., Clements J. A., Prescott L. F. Clinical pharmacokinetics of paracetamol. Clinical Pharmacokinetics, 1982, vol. 7, no. 2, pp. 93–107. https://doi.org/10.2165/00003088-198207020-00001

The authors declare that there are no conflicts of interest present.