Hoficin and remaxol effects on metabolic intoxication and lipid peroxidation in patients with chronic non-calculous cholecystitis on the background of diffuse liver diseases


Cite item

Full Text

Abstract

Relevance. The effect of the combined use of hoficin and remaxol on the indicators of metabolic intoxication and lipid peroxidation was studied in patients with chronic non-calculous cholecystitis on the background of diffuse liver diseases. Materials and Methods. The effect of the combined use of hoficin and remaxol was studied in 63 patients diagnosed with chronic non-calculous cholecystitison the background of acute chronic diffuse liver disease (CDLD), aged 20 to 53 years. Patients, by random distribution by age, gender, and severity of the clinical course of chronic non-calculous cholecystitis against the background of сhronic diffuse liver damage, were divided into two equivalent groups–the analyzed group, according to which the combined use of hoficin and remaxol and the control group using conventional treatment, after which the results were compared. In patients in the analyzed group, the level of middle molecules (MM) and the concentration of lipid peroxidation (POL) products, final malonic dialdehyde (MDA) and intermediate diene conjugates (DC) in the blood serum were studied. The screening method of V.V. Nikolaichyk was used in the modification of Gabrilovich. To study the level of medium molecules, blood serum was obtained by centrifugation at 4000g for 15 minutes. The method is based on plasma purification from high-molecular peptides and proteins using trichloroacetic acid, a 10% solution, and then the level of medium-­molecular peptides in terms of absorption in a monochromatic light stream was determined using direct spectrophotometry (at a wavelength of 254 nm) of the liquid. Results and Discussion. The content of MDA in blood plasma was estimated by M. Ushiama et al. in reaction with thiobarbituric acid. The studies were carried out in dynamics–before and after treatment. In patients with chronic non-calculous cholecystitis, an increase in serum MM levels and an increase in the concentration of POL products is observed. The use of the herbal preparation hoficin in combination with remaxol contributes to the normalization of clinical and laboratory signs of the disease, normalization of POL products. Under the influence of hoficin in combination with remaxol, the metabolic intoxication syndrome is eliminated, which is manifested by a significant decrease in the level of medium-­weight molecules to the upper limit of the norm, that is, this indicator is completely normalized, and the positive effect of treatment is observed in the first group of patients, unlike patients of the second group, in addition, the relative metabolic constancy of the internal environment of the body is restored. Conclusion. Patients with chronic non-calculous cholecystitis against the background of diffuse liver diseases exhibit endogenous metabolic intoxication syndrome. Increased concentration of LPO products-­MDA and DC indicates activation of biomembrane lipid peroxidation. Including the herbal preparation Hoffitsin in combination with Remaxol in the general treatment course of these patients contributes to normalization of clinical and laboratory disease indicators, medium molecule levels decrease to normal, and LPO products-­MDA and DC normalize. Under the influence of Hoffitsin in combination with Remaxol, metabolic intoxication syndrome is eliminated and relative metabolic constancy of the body’s internal environment is restored.

About the authors

Julia N. Ryabenko

RUDN University

Email: eryabenko@yandex.ru
ORCID iD: 0009-0000-0308-4471
SPIN-code: 3666-4156
Moscow, Russian Federation

Elina B. Ryabenko

Pirogov Russian National Research Medical University

Author for correspondence.
Email: eryabenko@yandex.ru
ORCID iD: 0009-0005-0160-8813
SPIN-code: 1724-0698
Moscow, Russian Federation

References

  1. Tikhonov SV, Dekkanova VD, Vinnichuk SA, Fila TS, Bakulina NV. Obesity, non-alcoholic fatty liver disease, Covid‑19. Medical Council. 2021;5:76—83. doi: 10.21518/2079-701X‑2021‑5‑76‑83
  2. Lazebnik LB, Golovanova EV, Turkina SV, Raikhelson KL, Okovityy SV, Drapkina OM, Maev IV, Martynov AI, Roitberg GE, Khlynova OV, Abdulganieva DI, Alekseenko SA, Ardatskaya MD, Bakulin IG, Bakulina NV, Bueverov AO, Vinitskaya EV, Volynets GV, Eremina EYu, Grinevich VB, Dolgushina AI, Kazyulin AN, Kashkina EI, Kozlova IV, Konev YuV, Korochanskaya NV, Kravchuk YuA, Li E.D, Loranskaya ID, Makhov VM, Mekhtiev SN, Novikova VP, Ostroumova OD, Pavlov ChS, Radchenko VG, Samsonov AA, Sarsenbaeva AS, Sayfutdinov RG, Seliverstov PV, Sitkin SI, Stefanyuk OV, Tarasova LV, Tkachenko EI, Uspensky YuP, Fominykh YuA, Khavkin AI, Tsyganova YuV, Sharhun OO. Non-alcoholic fatty liver disease in adults: clinic, diagnostics, treatment. Guidelines for therapists, third version. Experimental and Clinical Gastroenterology. 2021;1(1):4—52. doi: 10.31146/1682-8658‑ecg‑185‑1‑4‑52 (In Russian)
  3. Safarova HI. Diffuse liver lesions. The Eurasian Union of Scientists. 2019;12(2):13—20. doi: 10.31618/ESU.2413-9335.2019.2.69.486
  4. Carr RM, Oranu A, Khungar V. Non-alcoholic fatty liver disease: Pathophysiology and management. Gastroenterol Clin North Am. 2016;45(4): 639—52. doi: 10.1016/j.gtc.2016.07.003
  5. EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. Hepatol. 2016;64(6):1388—402. doi: 10.1016/j.jhep.2015.11.004
  6. Kapil S, Duseja A, Sharma BK, Singla, B, Chakraborti, A, Das A, Chawla Y. Small intestinal bacterial overgrowth and toll-like receptor signaling in patients with non-alcoholic fatty liver disease. Gastroenterol Hepatol. 2016;31(1):213—21. doi: 10.1111/jgh.13058
  7. Sorbi D, Boynton J, Lindor KD. The ratio of aspartate aminotransferase to alanine aminotransferase: potential value in differentiating non-alcoholic steatohepatitis from alcoholic liver disease. Am J. Gastroenterol. 1999;94(4):1018—22. doi: 10.1111/j.1572-0241.1999.01006.x
  8. Cerovic I, Mladenovic D, Jesic R, Naumović T, Branković M, Vučević D, Radosavljević T. Alcoholic liver disease/nonalcoholic fatty liver disease index: distinguishing alcoholic from nonalcoholic fatty liver disease. Eur J. Gastroenterol Hepatol. 2013;25(8):899—904. doi: 10.1097/MEG.0b013e32835f0786
  9. Mirzakarimova DB, Abdukodirov ST. Biochemical and morphological manifestations of liver damage in the treatment of toxic hepatitis. Economics and Society. 2022;3:363—366. doi: 10.46566/2225-1545_2022_1_94_363
  10. Stelmakh VV, Kovalenko AL, Popova VB, Uspensky YuP, Morozov VG, Belikova TN, Rafalsky VV, Antonova EA. The results of a multicenter open-label comparative randomized phase III trial in patients with intrahepatic cholestasis syndrome in chronic diffuse liver diseases. Therapeutic archive. 2021;93(12):1470—1476. doi: 10.26442/00403660.2021.12.201266 (In Russian)
  11. Pecherskikh MV, Efremova LI. The possibilities of preventing structural changes in the liver in patients with chronic non-calculous cholecystitis. Medical alphabet. 2021;20:21—24. doi: 10.33667/2078‑5631‑2021‑20‑21‑24 (In Russian)
  12. Ascha MS, Hanouneh IA, Lopez R, Tamimi TA-R, Feldstein AF, Zein NN. The incidence and risk factors of hepatocellular carcinoma in patients with nonalcoholic steatohepatitis. Hepatol. 2010;51(6):1972—78. doi: 10.1002/hep.23527
  13. Barsukova MA, Dmitriev LS, Yakubenko ED, Khomutov EV. Optimization of the protein precipitation regime in the determination of medium-­weight molecules as a marker of endogenous intoxication. University Clinic. 2021;1(38):46—53. doi: 10.26435/UC.V0I1(38).656
  14. David SA, Sil D. Development of Small-­Molecule Endotoxin Sequestering Agents. Sub-cellularbiochemistry. 2010;53:255—283. doi: 10.1007/978‑90‑481‑9078‑2_12
  15. Eslam M, Newsome PN, Anstee QM, Sarin ShK, Targher G, Romero-­Gomez M, Zelber-­Sagi Sh, Wai-­Sun Wong V, Dufour J-F, Schattenberg Jörn M, Kawaguchi T, Arrese M, Valenti L, Shiha G, Tiribelli C, Yki-­Järvinen H, Fan J-G, Grønbæk H, Yilmaz Y, Cortez-­Pinto H, Oliveira CP, Bedossa P, Adams LA. A new definition for metabolic associated fatty liver disease: an international expert consensus statement. Hepatol. 2020;73(1):202—09. doi: 10.1016/j.jhep.2020.03.039
  16. Maev IV, Samsonov AA, Lazebnik LB, Golovanova EV, Pavlov CS, Vovk EI, Ratziu V, Starostin KM. A new, non-invasive scale for steatosis developed using real-world data from Russian outpatients to aid in the diagnosis of non-alcoholic fatty liver disease. Adv Ther. 2020;37(11):4627—40. doi: 10.1007/s12325-020-01493‑w
  17. Leoni S, Tovoli F, Napoli L, Serio I, Ferri S, Bolondi L. Current guidelines for the management of non-alcoholic fatty liver disease: A systematic review with comparative analysis. World J. Gastroenterol. 2018;24(30):3361—73. doi: 10.3748/wjg.v24.i30.3361
  18. Ivashkin VT, Maev IV, Shulpekova YuO, Baranskaya YeK, Okhlobystin AV, Trukhmanov AS, Lapina TL, Sheptulin AA. Clinical recommendations of the Russian Gastroenterological Association for the diagnosis and treatment of biliary dyskinesia. Russian Journal of Gastroenterology, Hepatology, and Coloproctology. 2018;3:63—80. doi: 10.22416/1382‑4376‑2018‑28‑3‑63‑80
  19. Tilg H, Moschen AR. Evolution of inflammation in nonalcoholic fatty liver disease: The multiple parallel hits hypothesis. Hepatology. 2010;52(5):1836—46. doi: 10.1002/hep.24001
  20. Buzzetti E, Pinzani M, Tsochatzis EA. The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD). Metabolism. 2016;65(8):1038—48. doi: 10.1016/j.metabol.2015.12.012
  21. Nier A, Engstler AJ, Maier IB, Bergheim I. Markers of intestinal permeability are already altered in early stages of non-alcoholic fatty liver disease: Studies in children. PLoS One. 2017;12(9):101—371. doi: 10.1371/journal.pone.0183282
  22. Gridchik IE, Kurdyakov AV, Matveev AI. Experience of using the hepatoprotector remaxol in the treatment of liver cirrhosis. Experimental and clinical pharmacology. 2015;78(12):11—14. doi: 10.30906/0869‑2092‑2015‑78‑12‑11‑14
  23. Sas EI, Grinevich VB. Multicomponent infusion hepatoprotectors for drug-induced liver damage. Medical Council. 2019;3:84—88. doi: 10.21518/2079-701X‑2019‑3‑84‑88
  24. Stelmakh VV, Nekrasova AS, Kozlov VK, Kotiv MYa, Karpenko MN. The effectiveness of combination therapy with succinate-­containing drugs for non-alcoholic fatty liver disease. Clinical medicine. 2016;94(11):836—842. doi: 10.18821/0023‑2149‑2016‑94‑11‑836‑842
  25. Sviridov SV, Butrov AV, Afanasyev VV, Orlov YuP, Petrov AYu. The success of succinates and the prospects for use in critical conditions. Antibiotics and chemotherapy. 2024;69(7—8):80—91. doi: 10.37489/0235‑2990‑2024‑69‑7‑8‑80‑91
  26. Pang J, Xu W, Zhang XG, Wong L-H, Chan AW-H, Chan H-Y, Tse C-H, Shu SS-T, Choi PC—LH, Chan L-Y, Yu J, Wong VW-S. Significant positive association of endoto xemia with histological severity in 237 patients with nonalcoholic fatty liver disease. Aliment Pharmacol Ther. 2017;46(2):175—82. doi: 10.1111/apt.14119
  27. Speliotes EK, Yerges-­Armstrong LM, Wu J, Hernaez R, Kim LJ, Palmer CD, Gudnason V, Eiriksdottir G, Garcia ME, Nalls MA, Clark JM, Shuldiner AR, Butler JL, Tomas M, Hoffmann U. Genome-wide association analysis identifies variants associated with nonalcoholic fatty liver disease that have distinct effects on metabolic traits. PLoS Genet. 2011;7(3):1001—324. doi: 10.1371/journal.pgen.1001324
  28. Anstee QM, Darlay R, Cockell S, Meroni M, Govaere O, Tiniakos D, Burt AD, Bedossa P, Palmer J, Liu Y-L, Aithal GP, Allison M, Vacca M, Invernizzi P, Ekstedt M, Valenti L, Day CP. Genome-wide association study of non-alcoholic fatty liver and steatohepatitis in a histologically characterised cohort. Hepatol. 2020;73(3):505—515. doi: 10.1016/j.jhep.2020.04.003
  29. Vasilyuk VB, Verved AB, Kovalenko AL, Faraponova MV, Syraeva GI. Assessment of the effect of individual characteristics of volunteers and regimens of administration on the pharmacokinetics of succinic acid in the composition of various drugs. Experimental and clinical pharmacology. 2022;85(7):23—31. doi: 10.30906/0869‑2092‑2022‑85‑7‑23‑31
  30. Semiserin VA, Karakozov AG, Malkuta MA, Zolotareva LA, Levchenko OB, Kalyagin IE, Eremin MN. Evaluation of the effectiveness of hepatoprotective monotherapy of non-alcoholic fatty liver disease in the stage of steatohepatitis with a drug based on succinic acid and methionine. Therapeutic Archive. 2016;2:58—63. doi: 10.17116/terarkh201688258-63
  31. Okovity SV. Combined use of hepatoprotectors. The attending physician. 2020;8:38—42. doi: 10.26295/OS.2020.65.19.005
  32. Mayev IV, Bordin DS, Ilchishina TA, Kucheryavy Yu A. The biliary continuum: an up-to-date view on diseases of the biliary tract. Medical advice. 2021;15:122—134. doi: 10.21518/2079-701X‑2021‑15‑122‑134
  33. Mikhaylenko KA, Ulitina NN, Fedicheva NA. Peculiarities of changes in biochemical parameters of patients with chronic cholecystitis. Trends in the development of science and education. 2018;37(5):35—38. doi: 10.18411/lj‑04‑2018‑118. (In Russian).
  34. Karlas T, Petroff D, Sasso M, Fan J-G, Mi Y-Q, Lédinghen V, Kumar M, Lupsor-­Platon M, Han K-H, Cardoso AC, Ferraioli G, Myers RP, Beaugrand M, Shen F, Badea R, Keim V. Individual patient data meta-analysis of controlled attenuation parameter (cap) technology for assessing steatosis. Hepatol. 2017;66(5):1022—30. doi: 10.1016/j.jhep.2016.12.022
  35. Younossi ZM, Loomba R, Anstee QM, Rinella ME, Bugianesi E, Marchesini G, Neuschwander-­Tetri BA, Serfaty L, Negro F, Caldwell SH, Ratziu V, Corey KE, Friedman SL, Abdelmalek MF, Harrison SA, Chalasani NP, George J. Diagnostic modalities for nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, and associated fibrosis. Hepatology. 2018;68(1):349—60. doi: 10.1002/hep.29721
  36. Hashimoto E, Yatsuji S, Tobari M, Taniai M, Torii N, Tokushige K, Shiratori K. Hepatocellular carcinoma in patients with nonalcoholic steatohepatitis. Gastroenterol. 2009;44(19):89—95. doi: 10.1007/s00535-008-2262‑x
  37. Alekseenko SA, Koltunov AS, Ageeva EA, Sergeeva AY. Comprehensive assessment of the effectiveness of remaxol in patients with steatohepatitis with hyperammonemia. Experimental and clinical pharmacology. 2020;83(5):24—28. doi: 10.30906/0869‑2092‑2020‑83‑5‑24‑28
  38. Stelmakh VV, Bakulin IG, Kovalenko AL, Kozlov VK. The effectiveness of remaxol in patients with alcoholic liver disease. Russian journal of experimental and clinical pharmacology.2022;85(6):25—31. doi: 10.30906/0869‑2092‑2022‑85‑6‑25‑31
  39. Tarasova LV, Tsyganova YuV, Sidyakina ES. The focus is on infusion therapy with polyionic succinate-­methionine complex in the treatment of non-alcoholic fatty liver disease. Pharmaceutical Library. 2021;28(2):105—109. doi: 10.18565/pharmateca.2021.2.105-109.
  40. Tarasova LV, Tsyganova Yu V. Therapy of non-alcoholic liver steatosis as an important factor in preventing complications of non-alcoholic fatty liver disease. Therapy. 2023;9(7):202—207. doi: 10.18565/therapy. 2023.7.202-206
  41. Eslam M, Sanyal AJ, George J MAFLD: a consensus-­driven proposed nomenclature for metabolic associated fatty liver disease. Gastroenterology. 2020;158(7):1999—2014. doi: 10.1053/j.gastro.2019.11.312
  42. Byrne CD, Targher G NAFLD: A multisystem disease. Hepatol. 2015;62(1): 47—64. doi: 10.1016/j.jhep.2014.12.012
  43. Sharma M, Mitnala S, Vishnubhotla RK, Mukherjeex R, Reddyk DN, Rao PN. The riddle of nonalcoholic fatty liver disease: Progression from nonalcoholic fatty liver to nonalcoholic steatohepatitis. Clin Exp Hepatol. 2015;5(2):147—58. doi: 10.1016/j.jceh.2015.02.002
  44. Wider B, Pittler MH, Thompson-­Coon J, Ernst E Artichoke leaf extract for treating hypercholesterolaemia. Cochrane Database Syst Rev. 2009;4:12—26. doi: 10.1002/14651858.CD003335.pub2
  45. Nikolaychik VV, Moin VM, Kirkovskiy VV, Mazur LI, Lobacheva GA. Way of definition of «average molecules». Lab Delo. 1989;(8):31—3. (In Russian)

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Согласие на обработку персональных данных с помощью сервиса «Яндекс.Метрика»

1. Я (далее – «Пользователь» или «Субъект персональных данных»), осуществляя использование сайта https://journals.rcsi.science/ (далее – «Сайт»), подтверждая свою полную дееспособность даю согласие на обработку персональных данных с использованием средств автоматизации Оператору - федеральному государственному бюджетному учреждению «Российский центр научной информации» (РЦНИ), далее – «Оператор», расположенному по адресу: 119991, г. Москва, Ленинский просп., д.32А, со следующими условиями.

2. Категории обрабатываемых данных: файлы «cookies» (куки-файлы). Файлы «cookie» – это небольшой текстовый файл, который веб-сервер может хранить в браузере Пользователя. Данные файлы веб-сервер загружает на устройство Пользователя при посещении им Сайта. При каждом следующем посещении Пользователем Сайта «cookie» файлы отправляются на Сайт Оператора. Данные файлы позволяют Сайту распознавать устройство Пользователя. Содержимое такого файла может как относиться, так и не относиться к персональным данным, в зависимости от того, содержит ли такой файл персональные данные или содержит обезличенные технические данные.

3. Цель обработки персональных данных: анализ пользовательской активности с помощью сервиса «Яндекс.Метрика».

4. Категории субъектов персональных данных: все Пользователи Сайта, которые дали согласие на обработку файлов «cookie».

5. Способы обработки: сбор, запись, систематизация, накопление, хранение, уточнение (обновление, изменение), извлечение, использование, передача (доступ, предоставление), блокирование, удаление, уничтожение персональных данных.

6. Срок обработки и хранения: до получения от Субъекта персональных данных требования о прекращении обработки/отзыва согласия.

7. Способ отзыва: заявление об отзыве в письменном виде путём его направления на адрес электронной почты Оператора: info@rcsi.science или путем письменного обращения по юридическому адресу: 119991, г. Москва, Ленинский просп., д.32А

8. Субъект персональных данных вправе запретить своему оборудованию прием этих данных или ограничить прием этих данных. При отказе от получения таких данных или при ограничении приема данных некоторые функции Сайта могут работать некорректно. Субъект персональных данных обязуется сам настроить свое оборудование таким способом, чтобы оно обеспечивало адекватный его желаниям режим работы и уровень защиты данных файлов «cookie», Оператор не предоставляет технологических и правовых консультаций на темы подобного характера.

9. Порядок уничтожения персональных данных при достижении цели их обработки или при наступлении иных законных оснований определяется Оператором в соответствии с законодательством Российской Федерации.

10. Я согласен/согласна квалифицировать в качестве своей простой электронной подписи под настоящим Согласием и под Политикой обработки персональных данных выполнение мною следующего действия на сайте: https://journals.rcsi.science/ нажатие мною на интерфейсе с текстом: «Сайт использует сервис «Яндекс.Метрика» (который использует файлы «cookie») на элемент с текстом «Принять и продолжить».