JOURNAL CONTENT
CONTACT

Submission of the manuscript is online via e-mail
ecgarticle@gmail.com or
cholerez@mail.ru

Tel: +7 903 250 5288

Editorial Correspondence e-mail
gastrossr@gmail.com


Publishing, Subscriptions, Sales and Advertising, Correspondence e-mail
journal@cniig.ru

Tel: +7 917 561 9505

THE RULES OF SUBMITTING AN ARTICLE

READ

Scimago Journal & Country Rank

SCImago Journal & Country Rank

EXPERIMENTAL GASTROENTEROLOGY

    1. Irkutsk Scientific Centre of Surgery and Traumatology (Irkutsk, Russian Federation)

    Keywords:peritoneal adhesions,abdominal cavity,MAP kinase,prevention,experimental studies

    Abstract:Objective: to study the efficacy of the new promising medication as a way of preventing peritoneal adhesions. Material and methods. Peritoneal adhesion process was simulated in 30 Wistar rats. Intraperitoneal injection of a sterile conjugate aqueous solution of 4- [4- (4-fluorophenyl) -2- (4-methylsulfylphenyl) -1H-imidazole-5-pyridine with polyvinylimidazole (main group) was chosen as prevention of adhesion formation. Saline solution was used for control group. The pronouncement of the adhesion process was determined by macroscopic rate scale and histologic examination on the day 7, 14, and 30. Results. Significant differences between comparing groups on the day 7, 14 and 30 were determined with the help of scoring system of the pronouncement of the adhesion process. The severity of the adhesion process in main group was lower than in the control group. Also, significant differences in the morphological structure of adhesions were noticed. Conclusion. We demonstrated the first experience in use of promising medication as a way to prevent adhesions. The conducted study showed that in main group adhesion formation was not progressing during 7 days while in control group active adhesion formation and vascularization were proceeding. Thus, the use of promising medication is an effective way to prevent peritoneal adhesions.

      1. Аюшинова Н. И., Шурыгина И. А., Шурыгин М. Г., Панасюк А. И. Современные подходы к профилактике спаечного процесса в брюшной полости// Сиб. мед. журн. (Иркутск). - 2011. - Т. 105, № 6. - С. 16-20.
      2. Lai K. N., Tang S. C.W., Leung J. C.K. Mediators of inflammation and fibrosis// Perit. Dial. Int. - 2007. - Vol. 27, Suppl 2. - S. 65-71.
      3. Ступин В. А., Мударисов Р. Р., Михайлусов С. В. и соавт. Комплексный подход в лечении и профилактике спаечной болезни брюшной полости и её осложнений. 11-й международный конгресс по эндоскопической хирургии; Апрель, 2007; Москва. Доступно по: http://valipatov.ru/?p=672 Ссылка активна на 16.01.2017
      4. HCIA Inc. Peritoneal adhesiolysis. National inpatients profile 1993. - Baltimore, 1994. - P. 653-655.
      5. Ray N. F., Larsen J. W., Stillman R. J., Jacobs R. J. Economic impact of hospitalizations for lower abdominal adhesiolysis in the United States in 1988// Surg. Gynecol. Obstet. - 1993. - Vol. 176. - P. 271-276.
      6. Compounds, pharmaceutical compositions and a method for the prophylaxis and treatment of the adhesion process: WO2012156938, application number: WO2012IB 52483 20120517, applicant(s): Joint Stock Company Pharmasyntez [ru]; Shurygin M. G. [RU]; Shurygina I. A. [RU].
      7. Аюшинова Н. И., Шурыгина И. А., Шурыгин М. Г. и соавт. Экспериментальная модель для разработки способов профилактики спаечного процесса в брюшной полости// Сиб. мед. журн. (Иркутск). - 2012. - Т. 109, № 2. - С. 51-53.
      8. Davey A. K., Maher P. J. Surgical adhesions: A timely update, a great challenge for the future// J. Minim. Invasive Gynecol. - 2007. - Vol. 14, N 1. - P. 15-22.
      9. Шурыгина И. А., Шурыгин М. Г., Зеленин Н. В., Гранина Г. Б. Роль MAP-киназных механизмов в регуляции клеточного роста// Сиб. мед. журн. (Иркутск). - 2009. - Т. 89, № 6. - С. 36-40.
      10. Drollette C. M., Badawy S. Z. A. Pathophysiology of pelvic adhesions: Modern trends in preventing infertility// J. Reprod. Med. - 1992.-Vol. 37. - P. 107-122.
      11. Шурыгина И. А., Шурыгин М. Г., Аюшинова Н. И., Каня О. В. Фибробласты и их роль в развитии соединительной ткани// Сиб. мед. журн. (Иркутск). - 2012. - Т. 110, № 3. - С. 8-12.
      12. De Cherney A. H., di Zerega G. S. Clinical problem of intraperitoneal postsurgical adhesion formation following general surgery and the use of adhesion prevention barriers// Surg. Clin. North Am. - 1997.-Vol. 77. - P. 671-688.
      13. Holmdahl L. Making and covering of surgical footprints// Lancet. - 1999. - Vol. 353. - P. 1456-1457.
      14. Dijkstra F. R., Nieuwenhuijzen M., Reijnen M. M. et al. Recent clinical developments in pathophysiology, epidemiology, diagnosis and treatment of intra-abdominal adhesions// Scand. J. Gastroenterol. - 2000. - Vol. 232. - P. 52-59.
      15. Rout U. K., Diamond M. P. Role of plasminogen activators during healing after uterine serosal lesioning in the rat// Fertil. Steril. - 2003. - Vol. 79, N 1. - P. 138-145.
     


    Full text is published :
    Shurygina I.A., Ajushinova N.I., Chepurnyh E.E., Shurygin M.G. METHOD OF PREVENTION OF ABDOMINAL CAVITY ADHESIVE DISEASE. Experimental and Clinical Gastroenterology Journal. 2017;146(10):83-87
    Read & Download full text

    1. The Chair of Military Therapy and the Chair of Military Toxicology and Medical Protection of Military Medical Academy of name S. М. Kirov (St. Petersburg, Russian Federation)

    Keywords:an experimental cirrhosis,dimethylnitrosamine,alcohol,treatment

    Abstract:Research objective: working out of model of a cirrhosis at animals, an estimation of its clinical-morphological features, studying of therapeutic efficiency of inosin glitsil-tsisteinil-glutamat dinatrium in comparison with ademetionin. Material and methods: Series of experiences (200 white rats), a chronic dimethylnitrosamine's intoxication (DMNA)) in different modes and alcohol within 3-4 weeks. Against a proceeding intoxication introduction of inosin glitsil-tsisteinil-glutamat dinatrium (10 or 30 mg/kg) or ademetionin (70 mg/kg) till 9 weeks. Through every week series from 7-8 animals weighed, estimated a condition of bodies of a belly cavity, visible vessels, presence of ascites. Samples of blood for the biochemical analysis and a liver for histological research took. Results: It is established that at introduction DMNA intraperitoneally in a dose of 10 mg/kg 3 times a week + ethanol in a dose of 3 g/kg (oral every other day) within 4 weeks naturally develop macroscopic (hepatomegaly, ascites, collaterals), biochemical and histological signs of a cirrhosis (a dystrophy of hepatocytes, endocellular cholestasis, the reaction of macrophages, expressed fibrosis, nodular reorganization, blood circulation infringements). Application with the medical purpose of ademetionin promoted regress of signs of a cirrhosis, but the fullest clinical-morphological answer has provided inosin glitsil-tsisteinil-glutamat dinatrium in a dose of 30 mg/kg. Conclusion: In the given research the adequate model of an experimental cirrhosis with a substantiation of conformity of the majority of criteria to a cirrhosis at the person is developed. The conclusion is drawn on high polyvalent therapeutic efficiency of inosin glitsil-tsisteinil-glutamat dinatrium and perspectivity of its application in clinical hepatology and toxicology.

      1. Гальперин Э. И. Получение цирроза печени и асцита в эксперименте. Экспериментальная хирургия, 1960, № 1, сс. 46-49.
      2. Костырев О. А. Роль регенераторных процессов в формировании экспериментального цирроза печени. Архив патологии, 1972, том 34, № 10, сс. 59-64.
      3. Венгеровский А. И. Фармакологические подходы к регуляции функций печени. Бюллетень сибирской медицины. 2002, № 1, сс. 25-28.
      4. Шалимов С. А., Радзиховский А. П., Кейсевич Л. В. Руководство по экспериментальной хирургии. - М.: Медицина, 1989, 272 с.
      5. Popper H. Histogenesis of alcoholic fibrosis and cirrhosis in the baboon. Am J Pathol., 1980, vol. 98, no. 3, pp. 695-716.
      6. Tsukamoto H., Matsuoka M., French S. Experimental models of hepatic fibrosis: a review. Semin. Liver Dis., 1990, vol. 10, no. 1, pp. 56-65.
      7. Lieber C. S. Interaction of ethanol with drugs, hepatotoxic agents, carcinogens and vitamins. Alcohol Alcohol., 1990, vol. 25, no. 2/3, pp. 157-176.
      8. Альперович Б. И., Орлов А. В., Киселева Ю. В. Возможности криодеструкции в лечении цирроза печени. Бюллетень сибирской медицины, 2004, № 2, сс. 79-85.
      9. Хабриев Р. У. Руководство по экспериментальному (доклиническому) изучению новых фармакологических веществ. - М.: Медицина, 2005, 832 с.
      10. Степанов А. В., Ярцева А. А., Гребенюк А. Н., Антонов В. Г., Антушевич А. Е. Экспериментальное обоснование применения иммуномодулятора моликсан в качестве средства терапии герпесвирусной инфекции. Военно-медицинский журнал, 2014, № 2, сс. 64-65.
      11. Гребенюк А. Н., Рейнюк В. Л., Антушевич А. Е., Халютин Д. А., Маркосян А. М. Эффективность гепатопротекторов пептидной и непептидной природы в терапии острых крайне тяжелых отравлений этиловым спиртом. Вестник Российской Военно-медицинской академии, 2014, № 1, сс. 136-141.
      12. Гребенюк А. Н., Рейнюк В. Л., Антушевич А. Е., Халютин Д. А. Эффективность гепатопротектора с пептидным компонентом моликсана при острой крайне тяжелой интоксикации этанолом. Токсикологический вестник, 2014, № 4, сс. 12-19.
      13. Filomeni G., Rotilio G., Ciriolo M. R. Cell signalling and the glutathione redox system. Biochem. Pharmacol., 2002, 64: pp. 1057-1064.
      14. Быстрова Ф. М., Буданова Е. Н. Перекись водорода и пероксиредоксины в редокс-регуляции внутриклеточной сигнализации. Биологические мембраны, 2007, том 24, № 2, сс. 115-125.
      15. Мартинович Г. Г., Черенкевич С. Н. Oкислительно-восстановительные процессы в клетках. - Минск: издательство «БГУ», 2008, 159 с.
      16. Ganzella M. et al. Intracerebroventricular administration of inosine is anticonvulsant against quinolinic acid-induced seizures in mice: an effect independent of benzodiazepine and adenosine receptors. Pharmacol Biochem Behav., 2011, vol. 100, № 2, pp. 271-274.
      17. Szabo G., Stumpf N., Radovits T. et al. Effects of inosine on reperfusion injury after heart transplantation. European Journal of Cardio-thoracic Surgery. 2006, vol. 30, no. 2, pp. 96-102.
      18. da Rocha Lapa F, da Silva MD, de Almeida Cabrini D, Santos AR. Anti-inflammatory effects of purine nucleosides, adenosine and inosine, in a mouse model of pleurisy: evidence for the role of adenosine A2 receptors. Purinergic Signal., 2012, Dec., vol. 8, no. 4, pp. 693-704.
      19. Módis K., Gerő D., Stangl R. et al. Adenosine and inosine exert cytoprotective effects in an in vitro model of liver ischemia-reperfusion injury. Int J Mol Med., 2013, Feb., vol. 31, no. 2, pp. 437-446.
      20. Nascimento F. P., Macedo-Júnior S.J., Pamplona F. A. Adenosine A1 receptor-dependent antinociception induced by inosine in mice: pharmacological, genetic and biochemical aspects. Mol Neurobiol., 2015, Jun., vol. 51, no. 3, pp. 1368-1778.
      21. Robin E., Saborium J., Maralac F., Raddatz E. Involvement of CD 73, equilibrative nucleoside transporters and inosine in rhythm and conduction disturbances mediated by adenosine A1 and A2A receptors in the developing heart. J Mol Cell Cardiol., 2013, Oct., vol. 63, no. 1, pp. 14-25.
      22. Welihinda A. A., Kaur M., Greene K., Zhai Y., Amento E. P. The adenosine metabolite inosine is a functional agonist of the adenosine A2A receptor with a unique signaling bias. Cell Signal., 2016, Feb., vol. 28, no. 6, pp. 552-560.
      23. Крутецкая 3. И. Участие комплекса ARP2/3 и белков WASP в действии глутоксима и моликсана на внутриклеточную концентрацию Са2+ в макрофагах. Доклады Академии Наук, 2015, том 464, № 2, сс. 227-230.
      24. Крутецкая 3. И. Ингибиторы фосфолипазы А2 модулируют влияние глутоксима и моликсана на внутриклеточный уровень Са2+ в макрофагах. Доклады Академии Наук, 2015, том 465, № 2, сс.1-3.
     


    Full text is published :
    Golofeevskiy V.Yu., Antushevich A.E., Antonov V.G., Grebeniuk A.N. NEW MODEL OF THE EXPERIMENTAL CIRRHOSIS FOR ESTIMATION HEPATOPROTECTIVE AND ANTIFIBROTIC EFFICIENCY OF DRUGS. Experimental and Clinical Gastroenterology Journal. 2017;146(10):88-93
    Read & Download full text

    1. Prenolica Limited, Biotechnology Company; Saint Petersburg State Forest Technical Academy (Moscow, Russian Federation)
    2. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Science (Moscow, Russian Federation)
    3. State Forest Technical University (Moscow, Russian Federation)

    Keywords:long-chain isoprenoid alcohols,polyprenols,dolichol,Ropren,Essentiale Forte,carbon tetrachloride,hepatocytes,liver function

    Abstract:The mechanism for the ability of pharmaceutical-grade plant long-chain isoprenoid alcohols (polyprenols) to improve liver function was investigated in a carbon tetrachloride animal model of liver damage. The pharmaceutical-grade polyprenol substance, Ropren®, was compared with a commonly used phospholipid substance, Essentiale Forte, for 21 days of treatment. The condition of hepatic cells and cellular membranes was investigated using electron and light microscopy. The study showed Ropren® restored liver function and morphology as soon as day 7-14 of treatment, an effect that was faster than improvement after treatment with Essentiale Forte. Similarly, levels of glycogen in the liver were restored faster after treatment with Ropren® than Essential Forte. Measurement of the activity of the membrane-bound enzymes, monoamine oxidase (MAO) and butyrylcholinesterase (BuChE) also showed Ropren® improved liver function by improving cellular membrane and mitochondrial membrane function. To our knowledge, these results show for the first time a mechanism of the stabilisation of cellular membranes after treatment with Ropren® along with improvements in liver enzymes. These functional improvements occur faster than Essentiale Forte, a commonly used hepatoprotector.

      1. Arima T, Okada Y, Kubota M, Nagata K, Higuchi Y. Tyramine oxidase activity in needle biopsy of normal livers and diseased livers. Enzyme, 1977;22(2):124-129.
      2. Bezborodkina NN, Okovityi SV, Kudriavtseva MV, Kirik OV, Zarubina IV, Kudriavtsev BN. Morphometry of hepatocyte mitochondrial apparatus in normal and cirrhotic rat liver. Tsitologiia, 2008;50(3):228-36.
      3. Castro JA, Diaz Gomez MI, de Ferreyra EC, de Castro CR, D’Acosta N, de Fenos CM. Differences in the carbon tetrachloride-induced damage to components of smooth and rough endoplasmic reticulum from rat liver. Biochemical and Biophysical Research Communications, 1973;50:337-343.
      4. Chojnacki T, Jankowski W, Swiezewska E. Dolichols and polyprenols: Elements of membranes, coenzymes and secondary metabolites. Cell Mol Biol Lett, 2001;6(2):192.
      5. Chojnacki T, Dallner G. The biological role of dolichol. Biochem J, 1988;251:1-9.
      6. Ciepichal E, Jemiola-Rzeminskab M, Hertela J, Swiezewska E, Strzalkab K. Configuration of polyisoprenoids affects the permeability and thermotropic properties of phospholipid/polyisoprenoid model membranes. Chemistry and Physics of Lipids, 2011;164:300-306.
      7. Ellman GL, Courtney KD, Andres VJr, Featherstone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol, 1961; 7:88-95.
      8. Fedotova J, Soultanov V, Nikitina T, Roschin V, Ordayn N and Hritcu L. Cognitive-enhancing activities of the polyprenol preparation Ropren® in gonadectomized 3-amyloid (25-35) rat model of Alzheimer’s disease. Physiol Behav, 2016;157:55-62.
      9. Fedotova J, Soultanov V, Nikitina T, Roschin V, Ordayn N. Ropren(®) is a polyprenol preparation from coniferous plants that ameliorates cognitive deficiency in a rat model of beta-amyloid peptide. Phytomedicine, 2012;19(5):451-6.
      10. Fowler CJ, Saaf J. Structure and functions of amine oxidases, Ed. B. Mondovi. Boca Raton, Florida, 1985, pp. 249-261.
      11. Gorkin VZ, Ovchinnikova LI. Amino oxidase system: recent achievements in researching the nature, functions and its disorders. Issues in Med Chem, 1993;39:2-10.
      12. Grundahl JEH, Guan Z, Rust S, Reunert J, Muller B, at al. Life with too much polyprenol-polyprenol reductase deficiency. Mol Genet Metab, 2012;105(4):642-651.
      13. Gundermann KI. The contemporary data on mechanism of action and clinical efficacy of essential phospholipids. Clin Gastroenterol Hepatol, 2002;3:21-24.
      14. Inage F, Furuhama K. Application of maximal removal rate of indocyanine green to the determination of hepatic functional mass in conscious rats. J Vet Med Sci, 1997;59(5):335-340.
      15. Ipatova OM, Torkhovskaya TI, Knyazev VA, Karuzina II et al. Comparative study of effect of Essentiale and new Russian hepatoprotector “Phospholiv” on a model of acute hepatitis in rats. Issues in Med Chem 1998;44(6):544-550.
      16. Janas T, Walinska K, Chojnacki T, Swiezewska E, Janas T. Modulation of properties of phospholipid membranes by the long-chain polyprenol (C(160)). Chem Phys Lipids, 2000;106:31-40.
      17. Khidrova NK, Shakhidoyatov Kh M. Plant polyprenols and their biological activity. Chem Nat Compd, 2002;38(2):107-121.
      18. Kurup RK, Kurup PA. Isoprenoid pathway - related membrane dysfunction in neuropsychiatric dicorders. Int J Neurosci, 2003;113(11):1579-1591.
      19. Lapteva EN, Atlas EE, Popova Yu R. Differentiated treatment in patients with metabolic syndrome and NASH, XX Russian Congress, Hepatology Today, Russian Journal of Gastroenterology, Hepatology and Coloproctology, 2015, no. 1.
      20. Lapteva EN, Roschin VI, Soultanov VS. Specific activity of polyprenol-based Ropren in toxic liver damage in a trial [in Russian]. Clinical Nutrition, 2006;1:25-29.
      21. Lapteva EN, Roschin VI, Soultanov VS. Specific activity of the polyprenols based therapeutic preparation Ropren (Bioeffective R) in experimental models of toxic liver damage. Clin Nutr, 2007;3:33-37.
      22. Lazarev SA, Lazareva DG, Kremleva OA. Experience of using therapeutic substance Ropren for treatment of hepatic toxicity of the I-II degree during chemotherapy (preliminary results), presented at the Russian scientific-practical conference: “High technology in oncology”, Barnaul, Altay Region, Russia, June 26-27, 2012.
      23. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem, 1951;193:265-275.
      24. Moralev SN, Rozengart EV. Comparative enzymology of cholinesterases. International University Lines. Biotechnology Series. No 6, La Jolla. California. USA. 2007, pp. 484.
      25. Obata T, Egashira T. Yamanaka Y. Changes in amine oxidase in plasma of rats treated with hepatotoxins. Jap J Pharmacol, 1988;48:142-144.
      26. Okovity SV. Clinical pharmacology of hepatoprotectors. Journal of Clinical Pharmacology and Rational Pharmacotherapy “Praktic”, March 2002; issue 3 (hepatology).
      27. Pronzato MA, Cottalasso D, Domenicotti C, Tenca C, Traverso N at al, Effects of CCl4 poisoning on metabolism of dolichol in rat liver microsomes and Golgi apparatus. Free Radic Res Commun, 1990;11(4-5):267-277.
      28. Roschin VI, Soultanov VS. Methods for processing vegetable raw materials. Patent RU 2238291, 2003a.
      29. Roschin VI, Soultanov VS. Preparation for stimulation of natural regeneration of liver. Patent RU 2252026, 2003b.
      30. Severina IS. On potential mechanism of selective inhibition by chlorgilyn and deprenyl of activity of mitochondrial monoamine oxidase of rats’ liver. Biokhimiya, 1979;44:195-204.
      31. Shabanov PD, Soultanov V. Pharmacology of polyprenol-containing drugs: focus on hepatoprotective, neuroprotective and anti-ischemic effects of ropren. The 15th International Congress “PHYTOPHARM-2011”, 25-27 July, 2011, Nuremberg, Germany, Abstract book, pp. 102-103.
      32. Shabanov PD, Sultanov VS, Roshchin VI, Nikitina TV, Lebedev AA, Bychkov ER, Proshin SN. Defensive effects of polyprenol-containing drug ropren in a model of subacute hepatosis with encephalopathy in rats. (23 ECNP Congress Amsterdam, 28 August to 1 September 2010) Eur Neuropsychopharmacol, 2010;20(Suppl. 3): S 237.
      33. Soultanov V. New hepatic and neurological clinical implications of long-chain plant polyprenols acting on the mammalian isoprenoid pathway. Eksp Klin Gastroenterol, 2016;135(11):104-113.
      34. Soultanov VS, Agishev VG, Monakhova IA, Mokhovikova IA, Kulikov AP, Roshchin VI, Nikitina TV. Ropren® improves liver and pancreatic function in patients with chronic alcoholism. Gastroenterology- Saint Petersburg, 2010a;4:12-18.
      35. Soultanov VS, Gavrisheva IA, Lapteva EN, Roschin VI. Use of Ropren in patients with chronic viral hepatitis. Development of scientific research and control of infectious diseases. Material of International Conference, St-Petersburg, 18-20 May, 2010b, pp.138-139.
      36. Soultanov VS, Fedotova J, Nikitina T, Roschin V, Ordyan N, Hritcu L. Antidepressant-like effect of Ropren® in | 3-amyloid-(25-35) rat model of Alzheimer’s disease with altered levels of androgens. Mol Neurobiol. 2017;54(4):2611-2621.
      37. Sun F-J and J-F Jia. Protective effect of polyprenols against acute liver injury induced by CCl4 and D-Gal. J Pharm Med 2015;3(1):17-21.
      38. Surmacz L, Swiezewska E. Polyisoprenoids - Secondary metabolites or physiologically important superlipids? Biochem Biophys Res Com, 2011;407;627-632.
      39. Sviderskii VL, Khovanskih AE, Rozengart EV, Moralev SN, et al. Comparative study of the effect of polyprenol therapeutic substance Ropren from conifer species on key enzymes of cholinergic and monoaminergic types of neurotransmission. Reports of the Science Academy, 2006;408(3):414-417.
      40. Sviderskii VL, Soultanov VS, Roscin VI, Khovansky AE, Rozergart EV. et al. Analysis of activity of polyprenol therapeutic substance Ropren and choline acetyl transferase drug Glyatilin on membrane-bound and “soluble” forms of choline esterase and monoamine oxidase in the brain and blood serum of rats on a model of hepatic encephalopathy induced by tetrachlormethane. Reports of Science Academy, 2007;412(3):412-416.
      41. Valtersson C, van Duijn G, Verkleij AJ, Chojnacki T, de Kruijff B, Dallner G. The influence of dolichol, dolichyl esters, and dolichyl phosphate on phospholipid polymorphism and fluidity in model membranes. J Biol Chem, 1985;260:2742-2751.
      42. Yang L, Wang CZ, Ye JZ, Li HT. Hepatoprotective effects of polyprenols from Ginkgo biloba L. leaves on CCl4-induced hepatotoxicity in rats. Fitoterapia, 2011;82:834-840.
      43. Zou ZS, Xin SJ, Li BS, Zhao JM et al. Relationship between cholinesterase, prothrombin activity and albumin and the pathology of the liver. Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi, 2001;15(4):349-351.
     


    Full text is published :
    Soultanov V.S., Sukhinin V.P., Roschin V.I., Rozengart E.V., Nikitina T.V. PLANT LONG-CHAIN ISOPRENOID ALCOHOLS (POLYPRENOLS) PROTECT LIVER VIA STABILISATION OF CELL MEMBRANES AND ORGANELLE STRUCTURE IN A CARBON TETRACHLORIDE ANIMAL MODEL OF TOXIC LIVER DAMAGE. Experimental and Clinical Gastroenterology Journal. 2017;146(10):94-101
    Read & Download full text

    1. Research Institute of Phthisiopulmonology at the Sechenov I. M. First Moscow State Medical University (Moscow, Russian Federation)
    2. Solagift Pty Ltd (St. Petersburg, Russian Federation)
    3. Saint Petersburg State Forest Technical University; Prenolica Limited, Biotechnology Company (Moscow, Russian Federation)

    Keywords:Ropren®,isoniazid,polyprenols,isoprenoid alcohols,tuberculosis,liver,hepatoprotector,neurotoxicity

    Abstract:Objectives. Treatment of tuberculosis (TB) with medications such as isoniazid may lead to antibacterial resistance, hepatotoxic and neurotoxic effects. The development of other methods of treatment for TB is needed. Ropren® is an established hepatoprotector and neuroprotector and was tested in isoniazid rat and mouse models. Methods. Analysis of liver function was performed in rats by measuring alanine aminotransferase (ALT), aspartate transaminase, (AST), total and direct bilirubin and alkaline phosphatase (AP). The condition of the liver (density, colour, elasticity and the condition of the front edge) was also recorded and hematoxylin and eosin stained sections were analysed. The distribution of dystrophic changes in hepatocytes was determined. Neurotoxicity was evaluated in mice by measuring the onset of seizures and the subsequent mortality rate of mice. Results. Ropren® (30 mg/kg, given concomitantly with isoniazid, total daily dose 75 mg/kg, over 14 days) protected the liver of rats from isoniazid toxicity. Loss of body weight in rats given 30 mg/kg doses of Ropren® was significantly less than in the control group and in the groups given 10 or 15 mg/kg doses of Ropren®. AST levels in rats given Ropren® (10, 15 and 30 mg/kg) were similar to levels in the control group. ALT levels decreased significantly in rats given 30 mg/kg of Ropren®. AP decreased significantly in rats given 10 and 15 mg/kg of Ropren®. The AP level in rats given 30 mg/kg Ropren® also decreased, but this was not statistically significant. Total and direct bilirubin levels were similar in treated and control rats. Rat livers from the control and experimental groups showed reduced elasticity and a colour change. Rats given 30 mg/kg Ropren® had a decrease in the weight index compared to the control group. There was a significant decrease in the degree of dystrophy in hepatocytes in rats given Ropren®. Hepatoprotective effects were more pronounced at 10 and 30 mg/kg Ropren®. Ropren® (20 and 100 mg/kg) given 40 minutes prior to isoniazid (200 mg/kg) delayed the onset of seizures in mice and improved survival rate. Conclusion. Ropren® reduced isoniazid toxicity and had a protective effect on the liver. Ropren (20 mg/kg) also had a neuroprotective effect. Ropren® should be considered as an adjuvant treatment for TB in humans, where it could be used concomitantly with current established therapies.

      1. CDC. US Government. Morbidity and Mortality Weekly Report (MMWR). Severe isoniazid-associated liver injuries among persons being treated for latent tuberculosis infection - United States, 2004-2008, vol. 59(08), pp. 224-229, March 5, 2010.
      2. Desai V. A., Agarwal S. B. Isoniazid Toxicity. Journal Indian Academy of Clinical Medicine, vol. 5, no. 1, pp. 83-85, 2004.
      3. Mirlohi M-S., Ekrami A., Shirali S., Ghobeishavi M., Pourmotahari F. Hematological and liver toxicity of anti-tuberculosis drugs. Electronic Physician, vol. 8, no. 9, pp. 3005-3010, 2016.
      4. Saukkonen J. J., Cohn D. L., Jasmer R. M., Schenker S., Jereb J. A., Nolan C. M., Peloquin C. A., Gordin F. M., Nunes D., Strader. D. B, Bernardo J., Venkataramanan R., Sterling T. R., on behalf of the ATS Hepatotoxicity of Antituberculosis Therapy Subcommittee. American Thoracic Society Documents. An official ATS statement: Hepatotoxicity of antituberculosis. American Journal of Respiratory and Critical Care Medicine, vol. 174, pp. 935-952, 2006.
      5. Attri S, Rana S. V., Vaiphei K, Sodho C. P., Katyal R., Goel R. C., Nain C. K., Singh K. Isoniazid- and rifampicin-induced oxidative hepatic injury - protection by N-acetylcysteine. Human & Experimental Toxicology, vol. 19, pp. 517-522, 2000.
      6. Devarbhavi H. Antituberculous drug-induced liver injury: current perspective. Tropical Gastroenterology, vol. 32, no. 3, pp. 167-174, 2011.
      7. D’Orazio J. L. Medscape. Isoniazid toxicity. July 14, 2016.
      8. National Institutes of Health. U. S. Department of Health & Human Services. Isoniazid. December 6, 2016.
      9. Tostmann A., Boeree M. J., Aarnoutse R. E., de Lange W. C.M., van der Ven A. J. A. M., Dekhuijzen R. Antituberculosis drug-induced hepatotoxicity: concise up-to-date review. Journal of Gastroenterology and Hepatology, vol. 23 pp. 192-202, 2008.
      10. Ohno M., Yamaguchi I., Yamamoto I., Fukuda T., Yokota S., Maekura R., Ito M., Yamamoto Y., Ogura T., Maeda K., Komuta K., Igarashi T., Azuma J. Slow N-acetyltransferase 2 genotype affects the incidence of isoniazid and rifampicin induced hepatotoxicity. International Journal of Tuberculosis and Lung Disease, vol. 4, no.3, pp.256-61, 2000.
      11. Arbex M. A., Varella Mde C., Siqueira H. R., Mello F. A. Antituberculosis drugs: Drug interactions, adverse effects, and use in special situations. Part 2: Second-line drugs. Journal Brasileiro de Pneumologia, vol. 10, no. 5, pp.641-656, 2010.
      12. Bharat A., Vedkumar M., Subhash H. S., Abraham O. C., Mathai D. Antituberculous therapy - induced toxicity. Journal of the Association of Physicians of India, vol. 51, pp. 522-524, 2003.
      13. Mafukidze A. T., Calnan M., Furin J. Peripheral neuropathy in persons with tuberculosis. Journal of Clinical Tuberculosis and Other Mycobacterial Diseases, vol.2, pp. 5-11, 2016.
      14. Loeb C., Besio G., Mainardi P., Scotto P., Benassi E., Bo G. P. Liposome-entrapped gamma-aminobutyric acid inhibits isoniazid-induced epileptogenic activity in rats. Epilepsia, vol. 27, no. 2, pp. 98-102.
      15. Puri M. M., Kumar L., Vishwakarma P. D., Behera D. Seizures with single therapeuric dose of isoniazid. Indian Journal of Tuberculosis, vol. 59, no. 2, pp. 100-102.
      16. Gómez-Cansino R., Guzmán-Gutiérrez S. L., Campos-Lara M. G., Espitia-Pinzón C. I., Reyes-Chilpa R. Natural compounds from Mexican medicinal plants as potential drug leads for anti-tuberculosis drugs. Anais da Academia Brasileira de Ciências, vol. 89, no. 1, pp. 31-43, 2017.
      17. Gupta V. K., Kumar M. M., Bisht D., Kaushik A. Plants in our combating strategies against Mycobacterium tuberculosis: progress made and obstacles met. Pharmaceutical Biology, vol. 55, no. 1, pp. 1536-1544, 2017.
      18. Kahaliw W., Aseffa A., Abebe M., Teferi M., Engidawork E. Evaluation of the antimycobacterial activity of crude extracts and solvent fractions of selected Ethiopian medicinal plants. BMC Complementary and Alternative Medicine, vol. 17:143, 2017.
      19. Komape N. P. M., Bagla V. P., Kabongo-Kayoka P., Masoko P. Anti-mycobacteria potential and synergistic effects of combined crude extracts of selected medicinal plants used by Bapedi traditional healers to treat tuberculosis related symptoms in Limpopo Province, South Africa. BMC Complementary and Alternative Medicine, vol.17:128, 2017.
      20. Lall N., Kumara V., Meyer D., Gasa N., Hamilton C., Motlalepula M., Oosthuizen C. Journal of Ethnopharmacology, vol.194, pp.740-748, 2016.
      21. Adhvaryu M. R., Reddy N. M., Vakharia B. C. Prevention of hepatotoxicity due to anti tuberculosis treatment: A novel integrative approach. World Journal of Gastroenterology, vol. 14, no. 30, pp. 4753-4762, 2008.
      22. Dange S. V. Liv.52 in the prevention of hepatotoxicity in patients receiving antitubercular drugs: a meta-analysis. Indian Journal of Clinical Practice, vol. 21, no. 2, pp. 81-86, 2010.
      23. Fauziyah P. N., Sukandar E. Y., Ayuningtyas D. K. Combination effect of antituberculosis drugs and ethanolic extract of selected medicinal plants against multi-drug resistant mycobacterium tuberculosis isolates. Scientia Pharmaceutica, vol. 85:14, 2017.
      24. Singh D., Cho W. C., Upadhyay G. Drug induced liver toxicity and prevention by herbal antioxidants: an overview. Frontiers in Physiology, vol. 6, Article 363, 2016.
      25. Osidak L. V., Erman E. H., Cybalova L. S., Karpova L. S., Drinevkiy V. P., Zarubaev V. V., Suhinin V. P., Nekrasova V. B., Soultanov V. S. Clinical efficacy of therapeutic substances from pine and spruce needles. Family Health in the ХХ1 century. In: Materials of Х International Scientific Conference, pp. 354-356, Bangkok, Thailand, 2006.
      26. Suhinin V. P. Effect of chlorophyll preparations “Fitolon” and “conifer natural complex” on the course of influenza infection in mice. In: The study and application of therapeutic and preventive medicines based on natural biologically active substances, Redacted by V. G. Bespalov and V. B. Nekrasova, St Petersburg, Aesculapius, pp. 332-335, 2000.
      27. Fedotova J., Soultanov V., Nikitina T., Roschin V., Ordayn N. Ropren® is a polyprenol preparation from coniferous plants that ameliorates cognitive deficiency in a rat model of beta-amyloid peptide-(25-35)-induced amnesia. Phytomedicine, vol. 19, pp. 451-456, 2012.
      28. Fedotova J., Soultanov V., Nikitina T., Roschin V., Ordyan N., Hritcu L. Ropren treatment reverses anxiety-like behavior and monoamines levels in gonadectomized rat model of Alzheimer’s disease. Biomedicine & Pharmacotherapy, vol. 83, pp. 1444-1455, 2016.
      29. Soultanov V. S., Roschin V. I., Agishev V. G., Monakhova I. S., Mokhovikova I. A., Kulikov A. P., Nikitina T. V. Ropren treatment of patients with alcohol and narcotic intoxication complicated by chronic infection with Hepatitis B, Hepatitis C and HIV. In: International conference. Development of scientific research and management of infectious diseases, pp. 136-137, St-Petersburg, Russian Federation, 2010.
      30. Soultanov V, Fedotova J, Nikitina T, Roschin V, Ordyan N, Hritcu L. Antidepressant-like effect of Ropren® in β-amyloid-(25-35) rat model of Alzheimer’s disease with altered levels of androgens. Molecular Neurobiology, vol. 54, no. 4, pp. 2611-2621, 2017.
      31. Eggens I., Ekstrom T. J., Aberg F. Studies on the polyisoprenols, cholesterol and ubiquinone in highly differentiated human hepatomas. Journal of Experimental Pathology, vol. 71, no. 2, pp. 219-232, 1990.
      32. Soultanov, V. New hepatic and neurological clinical implications of long-chain plant polyprenols acting on the mammalian isoprenoid pathway. Experimental and Clinical Gastroenterology, vol. 135, no. 11, pp. 104-113, 2016.
      33. Zhang Q., Huang L., Zhang C., Xie P., Zhang Y., Ding S., Xu F. Synthesis and biological activity of polyprenols. Fitoterapia, vol. 106, pp. 184-193, 2015.
      34. Bergamini E., Bizzarri R., Cavallini G., Cerbai B., Chiellini E., Donati A., Gori Z., Manfrini A., Parentini I., Signori F., Tamburini I. Ageing and oxidative stress: A role for dolichol in the antioxidant machinery of cell membranes? Journal of Alzheimer’s Disease, vol. 6, pp. 129-135, 2004.
      35. Sun F-J., Jia J-F. Protective effect of polyprenols against acute liver injury induced by CCl4 and D-Gal. Journal of Pharmaceutical Medicine, vol. 3, no. 1, pp. 17-21, 2015.
      36. Lapteva E. N., Roschin V. I., Soultanov V. S. Specific activity of the polyprenols based therapeutic preparation Ropren (Bioeffective R) in experimental models of toxic liver damage. Clinical Nutrition, vol. 3, pp. 33-37, 2007.
      37. Shabanov P. D., Sultanov V. S., Roshchin V. I., Nikitina T. V., Lebedev A. A., Bychkov E. R., Proschin E. N. Defensive effects of polyprenol-containing drug ropren in a model of subacute hepatosis with encephalopathy in rats. European Neuropsychopharmacology, vol. 20, p. S 237, 2010.
      38. Golovanova Е. V., Shaposhnikova N. А., Petrakov А. V., Melkina Е. S., Soultanov V. The hepatoprotector Ropren for the treatment of patients with nonalcoholic steatohepatitis: а prospective observational study. Experimental and Clinical Gastroenterology, vol. 133, no. 9, pp. 71-76, 2016.
      39. Soultanov V. S., Roschin V. I., Lapteva E. N. Randomised double blind study of the efficacy and safety of the new plant origin substance, Ropren, in the treatment of diseases of the hepatobiliary system. St-Petersburg Gastroenterology, vol. 1-2, pp. 106-112, 2007.
      40. Khodanovich M., Glazacheva V., Pan E., Akulov A., Krutenkova E., Trusov V., Yarnykh V. MRI study of the cuprizone-induced mouse model of multiple sclerosis: demyelination is not found after co-treatment with polyprenols (long-chain isoprenoid alcohols). Journal of Physics: Conference Series, vol. 677(2016):012007, 2016.
      41. Sviderskii V. L., Sultanov V. S., Roshchin V. I., Khovanskikh A. E., at al. Analysis of the effect of the polyprenol preparation ropren and the choline alphoscerate preparation gliatilin on the membrane-bound and soluble forms of cholinesterases and monoamine oxidase of rat brain and serum in the tetrachloromethane model system of hepatic encephalopathy. Doklady Biochemistry and Biophysics, vol. 412, no. 1, pp. 33-36, 2007.
      42. Fedotova Iu. O., Sultanov V. S., Kuznetsova N. N., Roshchin V. I., Nikitina T. V. Effect of new polyprenol drug ropren on anxiety-depressive-like behavior in rats with experimental Alzheimer disease [Article in Russian]. Eksperimental’naia i Klinicheskaia Farmakologiia, vol. 73, no. 9, pp. 2-5, 2010.
      43. Fedotova J., Soultanov V., Nikitina T., Roschin V., Ordyan N., Hritcu L. Cognitive-enhancing activities of the polyprenol preparation Ropren® in gonadectomized β-amyloid (25-35) rat model of Alzheimer’s disease. Physiology & Behavior, vol. 157, pp. 55-62, 2016.
      44. Soultanov V. S., Shabanov P. D., Roshchin V. I. Ropren - the first polyprenol pharmaceutical drug in the world for the treatment of diseases of the liver and brain. Pharmaceutical Bulletin, vol. 2-3, pp. 35-47, 2012.
      45. Vasiliev, V. N., Roschin, V. I., Felece, S. Extracting compounds of Picea abies (L.) Karst. Rastiteinye Resursy, vol. 32, pp. 151-180, 1996.
      46. Avtandilov G. G. Introduction to quantitative pathological morphology. Meditsina Publishing House, Moscow [in Russian], p. 216, 1980.
     


    Full text is published :
    Mozhokina G.N., Elistratova N.A., Mikhailova L.P., Makarova O.V. PLANT LONG-CHAIN ISOPRENOID ALCOHOLS (POLYPRENOLS) DECREASE HEPATOTOXICITY AND NEUROTOXICITY CAUSED BY ISONIAZID, AN ANTI-TUBERCULOSIS DRUG. Experimental and Clinical Gastroenterology Journal. 2017;146(10):102-109
    Read & Download full text