Preview

Bulletin of the Medical Institute "REAVIZ" (REHABILITATION, DOCTOR AND HEALTH)

Advanced search

Nfluence of exogenous factors on the morphological structure of the liver (literature review and original research)

https://doi.org/10.20340/vmi-rvz.2025.4.MORPH.1

Abstract

Objective: to study the influence of exogenous factors on the morphological structure of the liver based on literature analysis and original experimental research.
Materials and methods. A literature review was conducted on drug-induced liver injury, alcoholic liver disease, and the effects of ammonia on hepatocytes. An experimental study was performed on male rats with modeling of metabolic disorders by administration of palm oil (30 mg/kg) for 8 weeks and dexamethasone (0.125 mg/kg) for 13 days. The effects of metformin (300 mg/kg) and vildagliptin (8 mg/kg) on morphological liver changes were studied.
Results. It was established that drugs cause various morphological liver changes: steatohepatitis, veno-occlusive disease, cholestasis, acute and chronic hepatitis, granulomatous hepatitis. Alcoholic liver disease is characterized by activation of lipogenesis, inhibition of β-oxidation of fatty acids, disruption of NADH/NAD+ redox balance, development of oxidative stress and hepatocyte apoptosis. Ammonia exerts cytotoxic effects by disrupting glutamate metabolism and the Krebs cycle. The experimental study revealed pronounced dystrophic changes with predominant fatty dystrophy in centrilobular zones in the control group. Vildagliptin application showed better results compared to metformin in restoring liver morphological structure.
Conclusion. Exogenous factors cause a complex of pathomorphological liver changes at cellular, tissue, and organ levels. Understanding the mechanisms of hepatotoxic action of various agents is necessary for developing effective methods of prevention and treatment of drug-induced liver injury.

About the Authors

A. V. Myazina
Vernadsky Crimean Federal University
Russian Federation

Anna V. Myazina, Cand. Sci. (Med.), Assistant Professor, Department of Normal Anatomy 
Author contributions: study concept and design, data acquisition, analysis, and interpretation.

Akademika Vernadskogo Ave., 4, Simferopol, 295007, Republic of Crimea


Competing Interests:

The authors declare no competing interests. 



E. Yu. Bibik
Saint Luka Lugansk State Medical University
Russian Federation

Elena Yu. Bibik, Dr. Sci. (Med.), Head of the Department of Fundamental and Clinical Pharmacology 
Author contributions: data analysis, final approval of the manuscript for publication.

50th Anniversary of the Defense of Luhansk Block, 1G, Lugansk, 291045, Luhansk People's Republic


Competing Interests:

The authors declare no competing interests. 



D. R. Bukhtoyarova
Saint Luka Lugansk State Medical University
Russian Federation

Dar'ya R. Bukhtoyarova, Senior Laboratory Assistant, Department of Fundamental and Clinical Pharmacology 
Author's contribution: article preparation, literature review and analysis.

50th Anniversary of the Defense of Luhansk Block, 1G, Lugansk, 291045, Luhansk People's Republic


Competing Interests:

The authors declare no competing interests. 



References

1. Kutsenko V., Peresada E., Seliverstov P. Lekarstvennye porazheniya pecheni. Sovremennoe sostoyanie problemy. Vrach. 2020; 31 (1): 69–75. (In Russ). https://doi.org/10.29296/25877305-2020-01-15

2. Karimov R.N., Yunusov A.A. Lekarstvenne porazheniya pecheni i aspekty primeneniya gepatoprotektorov v prakticheskoy meditsine. in Library. 2021; 21(1): 77–82. (In Russ).

3. Molostvova A.F., Khabirova G.I., Kharisova Yu.I., Salimova L.M. Lekarstvenne porazheniya pecheni - sovremennyy vzglyad na aktual'nuyu problemu. Vestnik sovremennoy klinicheskoy meditsiny. 2022;15(5):107-115. (In Russ). https://doi.org/10.20969/VSKM.2022.15(5).107-115

4. Vlasova A.V., Shubina Yu.F., Sychev D.A. Lekarstvennoe porazhenie pecheni, assotsiirovannoe s antibiotikami, u detey v kriticheskikh sostoyaniyakh: prospektivnoe nablyudatel'noe issledovanie. Bezopasnost' i risk farmakoterapii. 2024; 12(2): 155-166. (In Russ). https://doi.org/10.30895/2312-7821-2023-389

5. Ivashkin V.T., Baranovskiy A.Yu., Raykhel'son K.L., Pal'gova L.K., Maevskaya M.V., Kondrashina E.A., i dr. Lekarstvennye porazheniya pecheni (klinicheskie rekomendatsii dlya vrachey). Rossiyskiy zhurnal gastroenterologii, gepatologii, koloproktologii. 2019; 29(1): 101–131. (In Russ). https://doi.org/10.22416/1382-4376-2019-29-1-101-131

6. Sandler Yu.G., Vinnitskaya E.V., Saliev K.G., Khomeriki S.G., Khaymenova T. Yu. Lekarstvenne porazheniya pecheni, indutsirovanne nesteroidnymi protivovospalitel'nymi preparatami: lektsiya i klinicheskoe nablyudenie. Al'manakh klinicheskoy meditsiny. 2019; 47 (6): 579-591. (In Russ). https://doi.org/10.18786/2072-0505-2019-47-060

7. Borodina E.A., Stepchenko M.A. Otsenka gepatotoksichnosti, indutsirovannoy protivoopukholevoy terapiey, po dannym laboratornykh pokazateley. Vektor molodezhnoy meditsinskoy nauki. 2024;(3):14-19. (In Russ).

8. Sukhanov D.S., Timofeev E.V., Alekseeva Yu.S., Azovtsev D.Yu. Lekarstvenne porazheniya pecheni pri tuberkuleze. Mekhanizmy razvitiya i metody diagnostiki. Juvenis scientia. 2023; 9(1): 24-42. (In Russ). https://doi.org/10.32415/jscientia_2023_9_1_24-42

9. Stepanenko D.A., Goma T.V., Kozlova N.M. Alkogol'naya bolezn' pecheni: voprosy etiologii i vliyanie faktorov riska (obzor literatury). Baykal'skiy meditsinskiy zhurnal. 2023; 2(2): 20-29. (In Russ). https://doi.org/10.57256/2949-0715-2023-2-20-29

10. Tsuda T., Tada H., Tanaka Y., Nishida N., Yoshida T., Sawada T., et all. Amiodarone-induced reversible and irreversible hepatotoxicity: two case reports. Journal of Medical Case Reports. 2018; 12 (95). https://doi.org/10.1186/s13256-018-1629-8

11. Pereverzev A.P., Ostroumova O.D., Kochetkov A.I. Kholestaticheskiy variant lekarstvenno-indutsirovannogo porazheniya pecheni. Kachestvennaya klinicheskaya praktika. 2020;(3):61-74. (In Russ). https://doi.org/10.37489/2588-0519-2020-3-61-74

12. Bibik E.Yu., Saul A.S., Krivokolysko S.G., Oleynik I.S., Moiseeva I. Ya., Bukhtoyarova D. R., i dr. Issledovanie gepatotoksichnosti novykh proizvodnykh tsianotioatsetamida v khronicheskom eksperimente. Mezhdunarodnyy nauchno-issledovatel'skiy zhurnal. 2024; 2(140): 1-8. (In Russ). https://doi.org/10.23670/IRJ.2024.140.69

13. Ostroumova O.D., Pereverzev A.P., Pavleeva E.E., Romanovskiy R. R. Antibiotik-assotsiirovannoe lekarstvenno-indutsirovannoe porazhenie pecheni s kholestazom: aktualizatsiya problemy v epokhu COVID 19. Meditsinskiy alfavit. 2021; (1): 31–43. (In Russ). https://doi.org/10.33667/2078-5631-2021-1-31-43

14. Kochetkov A.I., Akimova E.S., Ostroumova O.D. Patogeneticheskie mekhanizmy lekarstvennykh povrezhdeniy pecheni. Sibirskoe meditsinskoe obozrenie. 2020; (6): 36-50. (In Russ). https://doi.org/10.20333/2500136-2020-6-36-50

15. Sriuttha P., Sirichanchuen B., Permsuwan U. Hepatotoxicity of Nonsteroidal Anti-Inflammatory Drugs: A Systematic Review of Randomized Controlled Trials. International journal of hepatology. 2018; 15:5253623. https://doi.org/10.1155/2018/5253623.

16. Sukhanov D.S., Alekseeva Yu.S, Timofeev E,V. Gepatotoksicheskoe deystvie i metabolizm protivotuberkuleznykh preparatov. Meditsina: teoriya i praktika. 2024; 8(2): 48-62. (In Russ). https://doi.org/10.56871/MTP.2023.90.21.007

17. Mikhnevich E. A., Raevnevoy T. G., Leonchik E. V., Golovko T. G., Pavlovicha T. P. Gepatotoksichnost' nesteroidnykh protivovospalitel'nykh sredstv u patsientov s podagroy. Meditsinskiy zhurnal. 2023; 3(85): 115-121. (In Russ). https://doi.org/10.51922/1818-426X.2023.3.115

18. Li Q., Chen F., Wang, F. The immunological mechanisms and therapeutic potential in drug-induced liver injury: lessons learned from acetaminophen hepatotoxicity. Cell and Bioscience. 2022; 12(1): 187. https://doi.org/10.1186/s13578-022-00921-4

19. Lazebnik L.B., Golovanova E.V., Khlynova O.V., Alekseenko S.A., Aryamkina O.L., Bakulin I.G., i dr. Lekarstvenne porazheniya pecheni (LPP) u vzroslykh. Eksperimental'naya i klinicheskaya gastroenterologiya. 2020;174(2): 29-54. (In Russ). https://doi.org/10.31146/1682-8658-ecg-174-2-29-54

20. Bueverov A.O., Bueverova E.L. Evolyutsiya predstavleniy o lekarstvennykh porazheniyakh pecheni. Eksperimental'naya i klinicheskaya gastroenterologiya. 2019;163(3): 89–96. (In Russ). https://doi.org/31146/1682-8658-ecg-163-3-89-96

21. Ivashkin V.T., Raykhel'son K.L., Pal'gova L.K., Maevskaya M.V., Gerasimova O. A., Kondrashina E. A., i dr. Lekarstvenne porazheniya pecheni u onkologicheskikh patsientov. Onkogematologiya. 2020;15(3):80–94. (In Russ).

22. Plotnikova E.Yu., Baranova E.N., Vorosova O.A., Karyagina M.S., Krasnov K. A. Lekarstvennaya bolezn' pecheni. Klinicheskiy sluchay tsirroza pecheni na fone priema nesteroidnykh protivovospalitel'nykh preparatov. Lechashchiy vrach. 2020;(2):28-34. (In Russ). https://doi.org/10.26295/OS.2020.67.71.005

23. Ostroumova O.D., Borisova E.V., Piksina G.F., Pavleeva E.E. Lekarstvenne porazheniya pecheni v praktike vracha pervichnogo zvena (obzor klinicheskikh rekomendatsiy). Meditsinskiy alfavit. 2020;(21):58-69. (In Russ). https://doi.org/10.33667/2078-5631-2020-21-58-68

24. Zhong T, Fan Y, Dong X-L, Guo X, Wong KH, Wong W-t., et all. An Investigation of the Risk Factors Associated With Anti-Tuberculosis DrugInduced Liver Injury or Abnormal Liver Functioning in 757 Patients With Pulmonary Tuberculosis. Frontiers in Pharmacology. 2021; 12: 708522. https://doi.org/10.3389/fphar.2021.708522

25. Ma J., Björnsson E.S., Chalasani N. Hepatotoxicity of Antibiotics and Antifungals and Their Safe Use in Hepatic Impairment. Seminars in Liver Disease. 2024; 44(2): 239-257. https://doi.org/10.1055/s-0044-1787062.

26. Pereverzev A.P., Ostroumova O.D., Golovina O.V., Filippova A.V., Pavleeva E. E. Lekarstvenno-indutsirovannoe porazhenie pecheni s kholestazom na fone priema nesteroidnykh protivovospalitel'nykh sredstv. Meditsinskiy alfavit. 2021;(23):37-48. (In Russ). https://doi.org/10.33667/2078-5631-2021-23-37-48

27. Tkachenko P.E., Ivashkin V.T., Maevskaya M.V. Prakticheskie rekomendatsii po korrektsii gepatotoksichnosti, indutsirovannoy protivoopukholevoy terapiey. Zlokachestvenne opukholi. 2023; 13(3): 69-82. (In Russ). https://doi.org/10.18027/2224-5057-2023-13^2-2-69-82

28. Sukhanov D.S., Timofeev E.V., Alekseeva Yu.S., Nagornova K.A. Farmakologicheskaya korrektsiya gepatotok-sichnosti, indutsirovannoy protivotuberkuleznymi preparatami. Lechashchiy Vrach. 2023; 2 (26): 40-46. (In Russ). https://doi.org/10.51793/OS.2023.26.2.006

29. Dolgushina A.I., Volchegorskiy I.A., Novoselov P.N., Ushkareva E.V., Olevskaya E.R., Kuznetsova A.S. Gepatotoksichnost' protivotuberkuleznykh preparatov. Eksperimental'naya i klinicheskaya gastroenterologiya. 2018; 8(156): 116-124. (In Russ). https://doi.org/10.31146/1682-8658-ecg-156-8-116-124

30. Yan C., Hu W., Tu J., Li J., Liang Q., Han S. Pathogenic mechanisms and regulatory factors involved in alcoholic liver disease. Journal of Translational Medicine. 2023; 21(1): 300. https://doi.org/10.1186/s12967-023-04166-8

31. Nevzorova M.S., Chepkasova N.I., Botalov N.S. Sovremenne predstavleniya ob alkogol'nom steatogepatite. Mezhdunarodnyy studencheskiy nauchnyy vestnik. 2018; 5. (In Russ).

32. Usanova A.A., Pavlov Ch.S., Kuzma F.M., Novikova E.K., Sergutova N. P. Aktual'nost' i epidemiologiya alkogol'noy bolezni pecheni. Sovremenne problemy nauki i obrazovaniya. 2023; 1. (In Russ). https://doi.org/10.17513/spno.32337

33. Kuzma F.M., Turankova T.A., Usanova A.A., Pavlov Ch.S. Sovremenne podkhody k diagnostike fibroza pri alkogol'noy bolezni pecheni. Doktor.Ru. 2019; 3(158): 21–26. (In Russ). https://doi.org/10.31550/1727-2378-2019-158-3-21-26

34. Polunina T.E. Alkogol'ne porazheniya pecheni. Farmateka. 2019; 26(2): 106–114. (In Russ). https://dx.doi.org/10.18565/pharmateca.2019.2.106-114

35. Feldstein A.E., Gores G.J. Apoptosis in alcoholic and nonalcoholic steatohepatitis. Frontiers in Bioscience-Landmark. 2015; (10): 3093–3099. https://doi.org/10.2741/1765

36. Pirogova I.Yu., Sinitsyn S.P., Chulkov V.S. Klinicheskaya effektivnost' preparata Geptrong u patsientov s nealkogol'noy bolezn'yu pecheni v real'noy klinicheskoy praktike (pilotnoe issledovanie). Eksperimental'naya i klinicheskaya gastroenterologiya. 2020; (12): 109-117. (In Russ). https://doi.org/10.31146/1682-8658-ecg-184-12-109-118

37. Okulova I.I., Suntsova N.A., Zhdanova O.B., Prilepskaya K.S., Perminova E. A., Chugaynov P. A., i dr. Alkogol' i pechen'. Mezhdunarodnyy studencheskiy nauchnyy vestnik. 2018; 2. (In Russ).

38. Ermolova T.V., Ermolov S.Yu., Belova A.A. Ammiak — novaya terapevticheskaya mishen' pri khronicheskikh zabolevaniyakh pecheni. Eksperimental'naya i klinicheskaya gastroenterologiya. 2020; 174(4): 24-30. (In Russ). https://doi.org/10.31146/1682-8658-ecg-176-4-24-30

39. Nadinskaya M.Yu., Maevskaya M.V., Bakulin I.G., Bessonova E.N., Bueverov A.O., Zharkova M.S., i dr. Diagnosticheskoe i prognosticheskoe znachenie giperammoniemii u patsientov s tsirrozom pecheni, pechenochnoy entsefalopatiey i sarkopeniey (soglashenie spetsialistov). Rossiyskiy zhurnal gastroenterologii, gepatologii, koloproktologii. 2024; 34(1): 85-100. (In Russ). https://doi.org/10.22416/1382-4376-2024-34-1-85-100

40. Golovanova E.V. Ammiak – aktual'naya problema vracha i patsienta v terapevticheskoy praktike. Terapiya. 2018; (2): 49-55. (In Russ).

41. Balcar L., Krawanja J., Scheiner B., Paternostro R., Simbrunner B., Semmler G., et all. Impact of ammonia levels on outcome in clinically stable outpatients with advanced chronic liver disease. JHEP Reports. 2023; 5(4): 100682. https://doi.org/10.1016/j.jhepr.2023.100682

42. Bakulin I.G., Shalikiani N.V. Patogenez alkogol'noy bolezni pecheni. Doktor.Ru. Gastroenterologiya. 2015; 12(113): 7-12. (In Russ).

43. Niu X., Zhu L., Xu Y., Zhang M., Hao Y., Ma L., et al. Global prevalence, incidence, and outcomes of alcohol related liver diseases: a systematic review and meta-analysis. BMC Public Health. 2023; 23(1): 859. https://doi.org/10.1186/s12889-023-15749-x

44. Sazonova A.A. Alkogol'naya bolezn' pecheni. Klinicheskoe nablyudenie. Aktual'ne issledovaniya. 2022; 50(129): 83-84. (In Russ).

45. Vyalov S.S. Endotoksiny, ammiak, zhirovaya bolezn' i fibroz pecheni. Doktor.Ru. 2018; 7 (151): 18–24. (In Russ). https://doi.org/10.31550/1727-2378-2018-151-7-18-24

46. Horrell J., Callaghan L., Dhanda A. Alcohol misuse in patients with alcohol-related liver disease: How can we do better? A narrative review of the literature. Alcohol, Clinical and Experimental Research. 2022; 46(8): 1364-1370. https://doi.org/10.1111/acer.14895


Review

For citations:


Myazina A.V., Bibik E.Yu., Bukhtoyarova D.R. Nfluence of exogenous factors on the morphological structure of the liver (literature review and original research). Bulletin of the Medical Institute "REAVIZ" (REHABILITATION, DOCTOR AND HEALTH). 2025;15(4):101-111. (In Russ.) https://doi.org/10.20340/vmi-rvz.2025.4.MORPH.1

Views: 2


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2226-762X (Print)
ISSN 2782-1579 (Online)