Список литературы

dongu-vestnik01.ru

Вестник Донецкого университета. Серия 01. Естественные науки

Vestnik of Donetsk University. Series 01. Natural Sciences

2415-7058

507

10.5281/zenodo.19179596

Articles

Статьи

Research Article

DYNAMICS OF LIPID METABOLISM INDICATORS IN RATS UNDER CHRONIC INTOXICATION WITH THIOACETAMIDE AND AGAINST THE BACKGROUND OF CORRECTION

ДИНАМИКА ПОКАЗАТЕЛЕЙ ЛИПИДНОГО ОБМЕНА ПРИ ХРОНИЧЕСКОЙ ИНТОКСИКАЦИИ ТИОАЦЕТАМИДОМ И НА ФОНЕ КОРРЕКЦИИ У КРЫС

https://orcid.org/0000-0002-7957-2399

Smolyankin

Denis Anatolyevich

Смолянкин

Денис Анатольевич

smolyankin.denis@yandex.ru 1

https://orcid.org/0009-0008-3068-3961

Khmel

Alexandra Olegovna

Хмель

Александра Олеговна

khmel.al01@gmail.com 2

https://orcid.org/0000-0002-1236-8246

Yakupova

Tatyana Georgievna

Якупова

Татьяна Георгиевна

tanya.kutlina.92@mail.ru 3

https://orcid.org/0000-0002-7321-0864

Gizatullina

Alina Anvarovna

Гизатуллина

Алина Анваровна

alinagisa@yandex.ru 4

https://orcid.org/0000-0001-5596-8180

Khusnutdinova

Nadezhda Yuryevna

Хуснутдинова

Надежда Юрьевна

h-n-yu@yandex.ru 5

https://orcid.org/0000-0001-8798-0846

Repina

Elvira Faridovna

Репина

Эльвира Фаридовна

e.f.repina@bk.ru 6

https://orcid.org/0000-0003-2677-0479

Ryabova

Yulia Vladimirovna

Рябова

Юлия Владимировна

ryabovaiuvl@gmail.com 7

https://orcid.org/0000-0003-0039-6757

Karimov

Denis Olegovich

Каримов

Денис Олегович

karimovdo@gmail.com 8

https://orcid.org/0000-0002-2995-310X

Gimadieva

Alfiya Raisovna

Гимадиева

Альфия Раисовна

alf_gim@mail.ru 9

Уфимский НИИ медицины труда и экологии человека Ufa research institute of occupational health and human ecology

Уфимский НИИ медицины труда и экологии человека; Национальный НИИ общественного здоровья имени Н.А. Семашко Ufa research institute of occupational health and human ecology; N.A. Semashko National Research Institute of Public Health

Уфимский федеральный исследователь¬ский центр Российской академии наук Ufa Institute of Chemistry UFRC RAS

10 04 2026

NO1 (2026)

№1 (2026)

101 116 17 04 2026

2026

Вестник Донецкого университета. Серия 01. Естественные науки

Vestnik of Donetsk University. Series 01. Natural Sciences

Эта статья распространяется на условиях лицензии Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)

This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0)

https://dongu-vestnik01.ru/index.php/bdsa/article/view/507

A comparative analysis of the effects of the hepatoprotectors ademetionine (ADM) and the complex compound MG-10 on lipid metabolism parameters was performed using a model of chronic thioacetamide (TAA) intoxication in rats. Enzymatic colorimetric analysis was used to determine the concentration of triglycerides (TG) and total cholesterol (TC) in blood serum on days 50 and 100. MG-10 was found to have a pronounced hypotriglyceridemic effect both at the intermediate and final stages of the study. By day 100, a statistically significant increase in TC was observed in the TAA+MG-10 group, while TG levels remained reduced. The use of ADM led to a less pronounced decrease in triglyceride levels. The results demonstrate the possible complex corrective effect of MG-10 on lipid metabolism in TAA-induced liver injury.

Проведена сравнительная оценка влияния гепатопротекторов, адеметионина (АДМ) и комплексного соединения МГ-10, с использованием модели хронической интоксикации крыс тиоацетамидом (ТАА), на показатели липидного обмена. Методом ферментативного колориметрического анализа в сыворотке крови определяли концентрацию триглицеридов (ТГ) и общего холестерина (ХСТ) на 50-е и 100-е сутки. Установлено, что МГ-10 оказывал выраженный гипотриглицеридемический эффект как на промежуточном, так и на заключительном этапе исследования. К 100-му дню в группе ТАА+МГ-10 выявлено статистически значимое повышение ХСТ при сохранении сниженного уровня ТГ. Применение АДМ приводило к менее выраженному уменьшению содержания триглицеридов. Результаты демонстрируют возможное комплексное корригирующее влияние МГ-10 на метаболизм липидов при ТАА-индуцированном повреждении печени.

thioacetamide lipid metabolism triglycerides total cholesterol ademetionine MG-10 hepatoprotection chronic intoxication experimental model rats

тиоацетамид липидный обмен триглицериды общий холестерин адеметионин МГ-10 гепатопротекция хроническая интоксикация экспериментальная модель крысы

[Полный текст статьи отсутствует в исходных данных. Необходимо добавить текст из PDF или другого источника.]

Список литературы

1. Liu Z.P., Ouyang G.Q., Huang G.Z., Wei J., Dai L., He S.Q., Yuan G.D. Global burden of cirrhosis and other chronic liver diseases due to nonalcoholic fatty liver disease, 1990-2019 // World J. Hepatol. – 2023. – V. 15, No 11. – P. 1210-1225. – DOI: 10.4254/wjh.v15.i11.1210.

2. Gao B., Bataller R. Alcoholic liver disease: pathogenesis and new therapeutic targets // Gastroenterology. – 2011. – V. 141, No 5. – P. 1572-1585. – DOI: 10.1053/j.gastro.2011.09.002.

3. Gu X., Manautou J.E. Molecular mechanisms underlying chemical liver injury // Expert Rev. Mol. Med. – 2012. – V. 14. – P. e4. – DOI: 10.1017/S1462399411002110.

4. Pollard K.M., Christy J.M., Cauvi D.M., Kono D.H. Environmental Xenobiotic Exposure and Autoimmunity // Curr. Opin. Toxicol. – 2018. – V. 10. – P. 15-22. – DOI: 10.1016/j.cotox.2017.11.009.

5. Li Y., Fan H., Li B., Liu X. Environmental Impact of Xenobiotic Aromatic Compounds and Their Biodegradation Potential in Comamonas testosteroni // Int. J. Mol. Sci. – 2024. – V. 25, No 24. – P. 13317. – DOI: 10.3390/ijms252413317.

6. Miglani R., Parveen N., Kumar A., Ansari M.A., Khanna S., Rawat G., Panda A.K., Bisht S.S., Upadhyay J., Ansari M.N. Degradation of Xenobiotic Pollutants: An Environmentally Sustainable Approach // Metabolites. – 2022. – V. 12, No 9. – P. 818. – DOI: 10.3390/metabo12090818.

7. Kumar M., Sarma D.K., Shubham S., Kumawat M., Verma V., Prakash A., Tiwari R. Environmental Endocrine-Disrupting Chemical Exposure: Role in Non-Communicable Diseases // Front. Public Health. – 2020. – V. 8. – P. 553850. – DOI: 10.3389/fpubh.2020.553850.

8. Rai M., Paudel N., Sakhrie M., Gemmati D., Khan I.A., Tisato V., Kanase A., Schulz A., Singh A.V. Perspective on Quantitative Structure–Toxicity Relationship (QSTR) Models to Predict Hepatic Biotransformation of Xenobiotics // Livers. – 2023. – V. 3, No 3. – P. 448-462. – DOI: 10.3390/livers3030032.

9. Lerapetritou M.G., Georgopoulos P.G., Roth C.M., Androulakis L.P. Tissue-level modeling of xenobiotic metabolism in liver: An emerging tool for enabling clinical translational research // Clin. Transl. Sci. – 2009. – V. 2, No 3. – P. 228-237. – DOI: 10.1111/j.1752-8062.2009.00092.x.

10. Darenskiy D.I. Features of the development and treatment of lipid metabolism disorders in patients with metabolic dysfunction-associated steatotic liver disease: A review // Consilium Medicum. – 2025. – V. 27, No 10. – P. 594-603. – DOI: 10.26442/20751753.2025.10.203461.

11. Abdulhameed A.A.R., Lim V., Bahari H., Khoo B.Y., Abdullah M.N.H., Tan J.J., Yong Y.K. Adverse Effects of Bisphenol A on the Liver and Its Underlying Mechanisms: Evidence from In Vivo and In Vitro Studies // Biomed Res. Int. – 2022. – V. 2022. – P. 8227314. – DOI: 10.1155/2022/8227314.

12. Chakraborty S., Anand S., Numan M., Bhandari R.K. Ancestral bisphenol A exposure led to non-alcoholic fatty liver disease and sex-specific alterations in proline and bile metabolism pathways in the liver // Environ. Toxicol. Chem. – 2025. – V. 44, No 4. – P. 958-972. – DOI: 10.1093/etojnl/vgae081.

13. Roth K., Yang Z., Agarwal M., Liu W., Peng Z., Long Z., Birbeck J., Westrick J., Liu W., Petriello M.C. Exposure to a mixture of legacy, alternative, and replacement per- and polyfluoroalkyl substances (PFAS) results in sex-dependent modulation of cholesterol metabolism and liver injury // Environ. Int. – 2021. – V. 157. – P. 106843. – DOI: 10.1016/j.envint.2021.106843.

14. Foulds C.E., Treviño L.S., York B., Walker C.L. Endocrine-disrupting chemicals and fatty liver disease // Nat. Rev. Endocrinol. – 2017. – V. 13, No 8. – P. 445-457. – DOI: 10.1038/nrendo.2017.42.

15. Rudraiah S., Zhang X., Wang L. Nuclear Receptors as Therapeutic Targets in Liver Disease: Are We There Yet? // Annu. Rev. Pharmacol. Toxicol. – 2016. – V. 56. – P. 605–626. – DOI: 10.1146/annurev-pharmtox-010715-103209.

16. Meyer J.N., Leung M.C., Rooney J.P., Sendoel A., Hengartner M.O., Kisby G.E., Bess A.S. Mitochondria as a target of environmental toxicants // Toxicol. Sci. – 2013. – V. 134, No 1. – P. 1-17. – DOI: 10.1093/toxsci/kft102.

17. Mihajlovic M., Vinken M. Mitochondria as the Target of Hepatotoxicity and Drug-Induced Liver Injury: Molecular Mechanisms and Detection Methods // Int. J. Mol. Sci. – 2022. – V. 23, No 6. – P. 3315. – DOI: 10.3390/ijms23063315.

18. Barouki R., Samson M., Blanc E.B., Colombo M., Zucman-Rossi J., Lazaridis K.N., Miller G.W., Coumoul X. The exposome and liver disease - how environmental factors affect liver health // J. Hepatol. – 2023. – V. 79, No 2. – P. 492-505. – DOI: 10.1016/j.jhep.2023.02.034.

19. Beier J.I., Arteel G.E. Environmental exposure as a risk-modifying factor in liver diseases: Knowns and unknowns // Acta Pharm. Sin. B. – 2021. – V. 11, No 12. – P. 3768-3778. – DOI: 10.1016/j.apsb.2021.09.005.

20. Enciso N., Amiel J., Fabián-Domínguez F., Pando J., Rojas N., Cisneros-Huamaní C., Nava E., Enciso J. Model of Liver Fibrosis Induction by Thioacetamide in Rats for Regenerative Therapy Studies // Anal. Cell. Pathol. – 2022. – V. 2022. – P. 2841894. – DOI: 10.1155/2022/2841894.

21. Alshanwani A.R., Hagar H., Shaheen S., Alhusaini A.M., Arafah M.M., Faddah L.M., Alharbi F.M., Sharma A.K., Fayed A., Badr A.M. A promising antifibrotic drug, pyridoxamine attenuates thioacetamide-induced liver fibrosis by combating oxidative stress, advanced glycation end products, and balancing matrix metalloproteinases // Eur. J. Pharmacol. – 2022. – V. 923. – P. 174910. – DOI: 10.1016/j.ejphar.2022.174910.

22. Shaker M.E., Eisa N.H., Elgaml A., El-Mesery A., El-Shafey M., El-Dosoky M., El-Mowafy M., El-Mesery M. Ingestion of mannose ameliorates thioacetamide-induced intrahepatic oxidative stress, inflammation and fibrosis in rats // Life Sci. – 2021. – V. 286. – P. 120040. – DOI: 10.1016/j.lfs.2021.120040.

23. Shin M.R., Lee J.A., Kim M., Lee S., Oh M., Moon J., Nam J.W., Choi H., Mun Y.J., Roh S.S. Gardeniae Fructus Attenuates Thioacetamide-Induced Liver Fibrosis in Mice via Both AMPK/SIRT1/NF-κB Pathway and Nrf2 Signaling // Antioxidants. – 2021. – V. 10, No 11. – P. 1837. – DOI: 10.3390/antiox10111837.

24. Staňková P., Kučera O., Lotková H., Roušar T., Endlicher R., Cervinková Z. The toxic effect of thioacetamide on rat liver in vitro // Toxicol. In Vitro. – 2010. – V. 24, No 8. – P. 2097-2103. – DOI: 10.1016/j.tiv.2010.06.011.

25. Lo R.C., Kim H. Histopathological evaluation of liver fibrosis and cirrhosis regression // Clin. Mol. Hepatol. – 2017. – V. 23, No 4. – P. 302-307. – DOI: 10.3350/cmh.2017.0078.

26. Hammerich L., Tacke F. Hepatic inflammatory responses in liver fibrosis // Nat. Rev. Gastroenterol. Hepatol. – 2023. – V. 20, No 10. – P. 633-646. – DOI: 10.1038/s41575-023-00807-x.

27. Xie Y., Wang G., Wang H., Yao X., Jiang S., Kang A., Zhou F., Xie T., Hao H. Cytochrome P450 dysregulations in thioacetamide-induced liver cirrhosis in rats and the counteracting effects of hepatoprotective agents // Drug Metab. Dispos. – 2012. – V. 40, No 4. – P. 796-802. – DOI: 10.1124/dmd.111.043539.

28. Ingawale D.K., Mandlik S.K., Naik S.R. Models of hepatotoxicity and the underlying cellular, biochemical and immunological mechanism(s): a critical discussion // Environ. Toxicol. Pharmacol. – 2014. – V. 37, No 1. – P. 118-133. – DOI: 10.1016/j.etap.2013.08.015.

29. Ezhilarasan D. Molecular mechanisms in thioacetamide-induced acute and chronic liver injury models // Environ. Toxicol. Pharmacol. – 2023. – V. 99. – P. 104093. – DOI: 10.1016/j.etap.2023.104093.

30. Hajovsky H., Hu G., Koen Y., Sarma D., Cui W., Moore D.S., Staudinger J.L., Hanzlik R.P. Metabolism and toxicity of thioacetamide and thioacetamide S-oxide in rat hepatocytes // Chem. Res. Toxicol. – 2012. – V. 25, No 9. – P. 1955-1963. – DOI: 10.1021/tx3002719.

31. Wallace M.C., Hamesch K., Lunova M., Kim Y., Weiskirchen R., Strnad P., Friedman S.L. Standard operating procedures in experimental liver research: thioacetamide model in mice and rats // Lab. Anim. – 2015. – V. 49, No 1 Suppl. – P. 21-29. – DOI: 10.1177/0023677215573040.

32. Gong J., Tu W., Liu J., Tian D. Hepatocytes: A key role in liver inflammation // Front. Immunol. – 2023. – V. 13. – P. 1083780. – DOI: 10.3389/fimmu.2022.1083780.

33. Higashi T., Friedman S.L., Hoshida Y. Hepatic stellate cells as key target in liver fibrosis // Adv. Drug Deliv. Rev. – 2017. – V. 121. – P. 27-42. – DOI: 10.1016/j.addr.2017.05.007.

34. Luedde T., Kaplowitz N., Schwabe R.F. Cell death and cell death responses in liver disease: mechanisms and clinical relevance // Gastroenterology. – 2014. – V. 147, No 4. – P. 765-783.e4. – DOI: 10.1053/j.gastro.2014.07.018.

35. Zhou S., Gu J., Liu R., Wei S., Wang Q., Shen H., Dai Y., Zhou H., Zhang F., Lu L. Spermine Alleviates Acute Liver Injury by Inhibiting Liver-Resident Macrophage Pro-Inflammatory Response Through ATG5-Dependent Autophagy // Front. Immunol. – 2018. – V. 9. – P. 948. – DOI: 10.3389/fimmu.2018.00948.

36. Kisseleva T., Brenner D. Molecular and cellular mechanisms of liver fibrosis and its regression // Nat. Rev. Gastroenterol. Hepatol. – 2021. – V. 18, No 3. – P. 151-166. – DOI: 10.1038/s41575-020-00372-7.

37. Tsuchida T., Friedman S.L. Mechanisms of hepatic stellate cell activation // Nat. Rev. Gastroenterol. Hepatol. – 2017. – V. 14, No 7. – P. 397-411. – DOI: 10.1038/nrgastro.2017.38.

38. Roehlen N., Crouchet E., Baumert T.F. Liver Fibrosis: Mechanistic Concepts and Therapeutic Perspectives // Cells. – 2020. – V. 9, No 4. – P. 875. – DOI: 10.3390/cells9040875.

39. Fabregat I., Moreno-Càceres J., Sánchez A., Dooley S., Dewidar B., Giannelli G., Ten Dijke P. IT-LIVER Consortium. TGF-β signalling and liver disease // FEBS J. – 2016. – V. 283, No 12. – P. 2219-2232. – DOI: 10.1111/febs.13665.

40. Shirato T., Homma T., Lee J., Kurahashi T., Fujii J. Oxidative stress caused by a SOD1 deficiency ameliorates thioacetamide-triggered cell death via CYP2E1 inhibition but stimulates liver steatosis // Arch. Toxicol. – 2017. – V. 91, No 3. – P. 1319-1333. – DOI: 10.1007/s00204-016-1785-9.

41. Wei D.D., Wang J.S., Duan J.A., Kong L.Y. Metabolomic Assessment of Acute Cholestatic Injuries Induced by Thioacetamide and by Bile Duct Ligation, and the Protective Effects of Huang-Lian-Jie-Du-Decoction // Front. Pharmacol. – 2018. – V. 9. – P. 458. – DOI: 10.3389/fphar.2018.00458.

42. Farghali H., Canová N.K., Zakhari S. Hepatoprotective properties of extensively studied medicinal plant active constituents: possible common mechanisms // Pharmaceutical biology. – 2015. – V. 53, No 6. – P. 781-791. – DOI: 10.3109/13880209.2014.950387.

43. Полухина А.В., Винницкая Е.В., Сандлер Ю.Г., Хайменова Т.Ю. Адеметионин в лечении неалкогольной жировой болезни печени // Медицинский Совет. – 2017. – № 15. – С. 104-111. – DOI: 10.21518/2079-701X-2017-15-104-111.

44. Vergani L., Baldini F., Khalil M., Voci A., Putignano P., Miraglia N. New Perspectives of S-Adenosylmethionine (SAMe) Applications to Attenuate Fatty Acid-Induced Steatosis and Oxidative Stress in Hepatic and Endothelial Cells // Molecules (Basel, Switzerland). – 2020. – V. 25, No 18. – P. 4237. – DOI: 10.3390/molecules25184237.

45. Li H., Liu N.N., Peng Z.G. Effect of bicyclol on blood biomarkers of NAFLD: a systematic review and meta-analysis // BMJ open. – 2020. – V. 10, No 12. – P. e039700. – DOI: 10.1136/bmjopen-2020-039700.

46. Dludla P.V., Nkambule B.B., Mazibuko-Mbeje S.E., Nyambuya T.M., Marcheggiani F., Cirilli I., Ziqubu K., Shabalala S.C., Johnson R., Louw J., Damiani E., Tiano L. N-Acetyl Cysteine Targets Hepatic Lipid Accumulation to Curb Oxidative Stress and Inflammation in NAFLD: A Comprehensive Analysis of the Literature // Antioxidants (Basel, Switzerland). – 2020. – V. 9, No 12. – P. 1283. – DOI: 10.3390/antiox9121283.

47. Karedath J., Javed H., Ahsan Talpur F., Lal B., Kumari A., Kivan H., Anirudh Chunchu V., Hirani S. Effect of Vitamin E on Clinical Outcomes in Patients With Non-alcoholic Fatty Liver Disease: A Meta-Analysis // Cureus. – 2022. – V. 14, No 12. – P. e32764. – DOI: 10.7759/cureus.32764.

48. Мышкин В.А., Еникеев Д.А. Антиоксиданты пиримидиновой структуры в качестве средств коррекции перекисного окисления липидов, индуцированного токсическим фактором // Медицинский вестник Башкортостана. – 2014. – Т. 9, № 5. – С. 143-146.

49. Zuñiga-Aguilar E., Ramírez-Fernández O. Fibrosis and hepatic regeneration mechanism // Transl. Gastroenterol. Hepatol. – 2022. – V. 7. – P. 9. – DOI: 10.21037/tgh.2020.02.21.

50. Radun R., Trauner M. Role of FXR in Bile Acid and Metabolic Homeostasis in NASH: Pathogenetic Concepts and Therapeutic Opportunities // Semin. Liver Dis. – 2021. – V. 41, No 4. – P. 461-475. – DOI: 10.1055/s-0041-1731707.

51. Ebaid H., Bashandy S.A., Morsy F.A., Al-Tamimi J., Hassan I., Alhazza I.M. Protective effect of gallic acid against thioacetamide-induced metabolic dysfunction of lipids in hepatic and renal toxicity // J. King Saud Univ. Sci. – 2023. – V. 35, No 3. – P. 102531. – DOI: 10.1016/j.jksus.2022.102531.

52. Wu J., Gong L., Li Y., Qu J., Yang Y., Wu R., Fan G., Ding M., Xie K., Li F., Li X. Tao-Hong-Si-Wu-Tang improves thioacetamide-induced liver fibrosis by reversing ACSL4-mediated lipid accumulation and promoting mitophagy // J. Ethnopharmacol. – 2024. – V. 333. – P. 118456. – DOI: 10.1016/j.jep.2024.118456.

53. Aldini G., Altomare A., Baron G., Vistoli G., Carini M., Borsani L., Sergio F. N-Acetylcysteine as an antioxidant and disulphide breaking agent: the reasons why // Free Radic. Res. – 2018. – V. 52, No 7. – P. 751-762. – DOI: 10.1080/10715762.2018.1468564.

54. Zhitkovich A. N-Acetylcysteine: Antioxidant, Aldehyde Scavenger, and More // Chem. Res. Toxicol. – 2019. – V. 32, No 7. – P. 1318-1319. – DOI: 10.1021/acs.chemrestox.9b00152.

55. Myshkin V.А., Enikeyev D.А. Hepatoprotection against chemical influence: comparative effects of 5-hydroxy-6-methyluracil (oxymethyluracil), complex compound «oxymethyluracil + sodium succinate» and silymarine // Arch. Euromedica. – 2014. – V. 4, No 1. – P. 45-49.

56. Khazimullina Y.Z., Gimadieva A.R., Khairullina V.R., Kudoyarov E.R., Karimov D.O., Mustafin A.G. Synthesis and Study of the Hepatoprotective Activity of New Uracil Derivatives // Russ. J. Bioorg. Chem. – 2025. – V. 51. – P. 117-127. – DOI: 10.1134/S1068162025010157.

57. Waters N.J., Waterfield C.J., Farrant R.D., Holmes E., Nicholson J.K. Metabonomic deconvolution of embedded toxicity: application to thioacetamide hepato- and nephrotoxicity // Chem. Res. Toxicol. – 2005. – V. 18, No 4. – P. 639-654. – DOI: 10.1021/tx049869b.

58. Provost J.P., Hanton G., Net J.L. Plasma triglycerides: an overlooked biomarker of hepatotoxicity in the rat // Comp. Clin. Pathol. – 2003. – V. 12, No 2. – P. 95-101.

59. Horn P., Tacke F. Metabolic reprogramming in liver fibrosis // Cell Metab. – 2024. – V. 36, No 7. – P. 1439-1455. – DOI: 10.1016/j.cmet.2024.05.003.

60. Delgado M.E., Cárdenas B.I., Farran N., Fernandez M. Metabolic Reprogramming of Liver Fibrosis // Cells. – 2021. – V. 10, No 12. – P. 3604. – DOI: 10.3390/cells10123604.

61. Zhang D., Shi C., Wang Y., Guo J., Gong Z. Metabolic Dysregulation and Metabolite Imbalances in Acute-on-chronic Liver Failure: Impact on Immune Status // J. Clin. Transl. Hepatol. – 2024. – V. 12, No 10. – P. 865-877. – DOI: 10.14218/JCTH.2024.00203.

62. Zhang I.W., Curto A., López-Vicario C., Casulleras M., Duran-Güell M., Flores-Costa R., Colsch B., Aguilar F., Aransay A.M., Lozano J.J., Hernández-Tejero M., Toapanta D., Fernández J., Arroyo V., Clària J. Mitochondrial dysfunction governs immunometabolism in leukocytes of patients with acute-on-chronic liver failure // J. Hepatol. – 2022. – V. 76, No 1. – P. 93-106. – DOI: 10.1016/j.jhep.2021.08.009.

63. Saxena N., Chandra N.C. Cholesterol: A Prelate in Cell Nucleus and its Serendipity // Curr. Mol. Med. – 2020. – V. 20, No 9. – P. 692-707. – DOI: 10.2174/1566524020666200413112030.

64. Shi L., Chen H., Zhang Y., An D., Qin M., Yu W., Wen B., He D., Hao H., Xiong J. SLC13A2 promotes hepatocyte metabolic remodeling and liver regeneration by enhancing de novo cholesterol biosynthesis // EMBO J. – 2025. – V. 44, No 5. – P. 1442-1463. – DOI: 10.1038/s44318-025-00362-y.

REFERENCES

1. Liu, Z.P., Ouyang, G.Q., Huang, G.Z., Wei, J., Dai, L., He, S.Q. & Yuan, G.D. (2023) Global burden of cirrhosis and other chronic liver diseases due to nonalcoholic fatty liver disease, 1990-2019. World J. Hepatol. 15 (11), 1210-1225, doi: 10.4254/wjh.v15.i11.1210.

2. Gao, B. & Bataller, R. (2011) Alcoholic liver disease: pathogenesis and new therapeutic targets. Gastroenterology. 141 (5), 1572-1585, doi: 10.1053/j.gastro.2011.09.002.

3. Gu, X. & Manautou, J.E. (2012) Molecular mechanisms underlying chemical liver injury. Expert Rev. Mol. Med. 14, e4, doi: 10.1017/S1462399411002110.

4. Pollard, K.M., Christy, J.M., Cauvi, D.M. & Kono, D.H. (2018) Environmental Xenobiotic Exposure and Autoimmunity. Curr. Opin. Toxicol. 10, 15-22, doi: 10.1016/j.cotox.2017.11.009.

5. Li, Y., Fan, H., Li, B. & Liu, X. (2024) Environmental Impact of Xenobiotic Aromatic Compounds and Their Biodegradation Potential in Comamonas testosteroni. Int. J. Mol. Sci. 25 (24), 13317, doi: 10.3390/ijms252413317.

6. Miglani, R., Parveen, N., Kumar, A., Ansari, M.A., Khanna, S., Rawat, G., Panda, A.K., Bisht, S.S., Upadhyay, J. & Ansari, M.N. (2022) Degradation of Xenobiotic Pollutants: An Environmentally Sustainable Approach. Metabolites. 12 (9), 818, doi: 10.3390/metabo12090818.

7. Kumar, M., Sarma, D.K., Shubham, S., Kumawat, M., Verma, V., Prakash, A. & Tiwari, R. (2020) Environmental Endocrine-Disrupting Chemical Exposure: Role in Non-Communicable Diseases. Front. Public Health. 8, 553850, doi: 10.3389/fpubh.2020.553850.

8. Rai, M., Paudel, N., Sakhrie, M., Gemmati, D., Khan, I.A., Tisato, V., Kanase, A., Schulz, A. & Singh, A.V. (2023) Perspective on Quantitative Structure-Toxicity Relationship (QSTR) Models to Predict Hepatic Biotransformation of Xenobiotics. Livers. 3 (3), 448-462, doi: 10.3390/livers3030032.

9. Lerapetritou, M.G., Georgopoulos, P.G., Roth, C.M. & Androulakis, L.P. (2009) Tissue-level modeling of xenobiotic metabolism in liver: An emerging tool for enabling clinical translational research. Clin. Transl. Sci. 2 (3), 228-237, doi: 10.1111/j.1752-8062.2009.00092.x.

10. Darenskiy, D.I. (2025) Features of the development and treatment of lipid metabolism disorders in patients with metabolic dysfunction-associated steatotic liver disease: A review. Consilium Medicum. 27 (10), 594-603, doi: 10.26442/20751753.2025.10.203461.

11. Abdulhameed, A.A.R., Lim, V., Bahari, H., Khoo, B.Y., Abdullah, M.N.H., Tan, J.J. & Yong, Y.K. (2022) Adverse Effects of Bisphenol A on the Liver and Its Underlying Mechanisms: Evidence from In Vivo and In Vitro Studies. Biomed Res. Int. 2022, 8227314, doi: 10.1155/2022/8227314.

12. Chakraborty, S., Anand, S., Numan, M. & Bhandari, R.K. (2025) Ancestral bisphenol A exposure led to non-alcoholic fatty liver disease and sex-specific alterations in proline and bile metabolism pathways in the liver. Environ. Toxicol. Chem. 44 (4), 958-972, doi: 10.1093/etojnl/vgae081.

13. Roth, K., Yang, Z., Agarwal, M., Liu, W., Peng, Z., Long, Z., Birbeck, J., Westrick, J., Liu, W. & Petriello, M.C. (2021) Exposure to a mixture of legacy, alternative, and replacement per- and polyfluoroalkyl substances (PFAS) results in sex-dependent modulation of cholesterol metabolism and liver injury. Environ. Int. 157, 106843, doi: 10.1016/j.envint.2021.106843.

14. Foulds, C.E., Treviño, L.S., York, B. & Walker, C.L. (2017) Endocrine-disrupting chemicals and fatty liver disease. Nat. Rev. Endocrinol. 13 (8), 445-457, doi: 10.1038/nrendo.2017.42.

15. Rudraiah, S., Zhang, X. & Wang, L. (2016) Nuclear Receptors as Therapeutic Targets in Liver Disease: Are We There Yet? Annu. Rev. Pharmacol. Toxicol. 56, 605-626, doi: 10.1146/annurev-pharmtox-010715-103209.

16. Meyer, J.N., Leung, M.C., Rooney, J.P., Sendoel, A., Hengartner, M.O., Kisby, G.E. & Bess, A.S. (2013) Mitochondria as a target of environmental toxicants. Toxicol. Sci. 134 (1), 1-17, doi: 10.1093/toxsci/kft102.

17. Mihajlovic, M. & Vinken, M. (2022) Mitochondria as the Target of Hepatotoxicity and Drug-Induced Liver Injury: Molecular Mechanisms and Detection Methods. Int. J. Mol. Sci. 23 (6), 3315, doi: 10.3390/ijms23063315.

18. Barouki, R., Samson, M., Blanc, E.B., Colombo, M., Zucman-Rossi, J., Lazaridis, K.N., Miller, G.W. & Coumoul, X. (2023) The exposome and liver disease - how environmental factors affect liver health. J. Hepatol. 79 (2), 492-505, doi: 10.1016/j.jhep.2023.02.034.

19. Beier, J.I. & Arteel, G.E. (2021) Environmental exposure as a risk-modifying factor in liver diseases: Knowns and unknowns. Acta Pharm. Sin. B. 11 (12), 3768-3778, doi: 10.1016/j.apsb.2021.09.005.

20. Enciso, N., Amiel, J., Fabián-Domínguez, F., Pando, J., Rojas, N., Cisneros-Huamaní, C., Nava, E. & Enciso, J. (2022) Model of Liver Fibrosis Induction by Thioacetamide in Rats for Regenerative Therapy Studies. Anal. Cell. Pathol. 2022, 2841894, doi: 10.1155/2022/2841894.

21. Alshanwani, A.R., Hagar, H., Shaheen, S., Alhusaini, A.M., Arafah, M.M., Faddah, L.M., Alharbi, F.M., Sharma, A.K., Fayed, A. & Badr, A.M. (2022) A promising antifibrotic drug, pyridoxamine attenuates thioacetamide-induced liver fibrosis by combating oxidative stress, advanced glycation end products, and balancing matrix metalloproteinases. Eur. J. Pharmacol. 923, 174910, doi: 10.1016/j.ejphar.2022.174910.

22. Shaker, M.E., Eisa, N.H., Elgaml, A., El-Mesery, A., El-Shafey, M., El-Dosoky, M., El-Mowafy, M. & El-Mesery, M. (2021) Ingestion of mannose ameliorates thioacetamide-induced intrahepatic oxidative stress, inflammation and fibrosis in rats. Life Sci. 286, 120040, doi: 10.1016/j.lfs.2021.120040.

23. Shin, M.R., Lee, J.A., Kim, M., Lee, S., Oh, M., Moon, J., Nam, J.W., Choi, H., Mun, Y.J. & Roh, S.S. (2021) Gardeniae Fructus Attenuates Thioacetamide-Induced Liver Fibrosis in Mice via Both AMPK/SIRT1/NF-κB Pathway and Nrf2 Signaling. Antioxidants. 10 (11), 1837, doi: 10.3390/antiox10111837.

24. Staňková, P., Kučera, O., Lotková, H., Roušar, T., Endlicher, R. & Cervinková, Z. (2010) The toxic effect of thioacetamide on rat liver in vitro. Toxicol. In Vitro. 24 (8), 2097-2103, doi: 10.1016/j.tiv.2010.06.011.

25. Lo, R.C. & Kim, H. (2017) Histopathological evaluation of liver fibrosis and cirrhosis regression. Clin. Mol. Hepatol. 23 (4), 302-307, doi: 10.3350/cmh.2017.0078.

26. Hammerich, L. & Tacke, F. (2023) Hepatic inflammatory responses in liver fibrosis. Nat. Rev. Gastroenterol. Hepatol. 20 (10), 633-646, doi: 10.1038/s41575-023-00807-x.

27. Xie, Y., Wang, G., Wang, H., Yao, X., Jiang, S., Kang, A., Zhou, F., Xie, T. & Hao, H. (2012) Cytochrome P450 dysregulations in thioacetamide-induced liver cirrhosis in rats and the counteracting effects of hepatoprotective agents. Drug Metab. Dispos. 40 (4), 796-802, doi: 10.1124/dmd.111.043539.

28. Ingawale, D.K., Mandlik, S.K. & Naik, S.R. (2014) Models of hepatotoxicity and the underlying cellular, biochemical and immunological mechanism(s): a critical discussion. Environ. Toxicol. Pharmacol. 37 (1), 118-133, doi: 10.1016/j.etap.2013.08.015.

29. Ezhilarasan, D. (2023) Molecular mechanisms in thioacetamide-induced acute and chronic liver injury models. Environ. Toxicol. Pharmacol. 99, 104093, doi: 10.1016/j.etap.2023.104093.

30. Hajovsky, H., Hu, G., Koen, Y., Sarma, D., Cui, W., Moore, D.S., Staudinger, J.L. & Hanzlik, R.P. (2012) Metabolism and toxicity of thioacetamide and thioacetamide S-oxide in rat hepatocytes. Chem. Res. Toxicol. 25 (9), 1955-1963, doi: 10.1021/tx3002719.

31. Wallace, M.C., Hamesch, K., Lunova, M., Kim, Y., Weiskirchen, R., Strnad, P. & Friedman, S.L. (2015) Standard operating procedures in experimental liver research: thioacetamide model in mice and rats. Lab. Anim. 49 (1 Suppl), 21-29, doi: 10.1177/0023677215573040.

32. Gong, J., Tu, W., Liu, J. & Tian, D. (2023) Hepatocytes: A key role in liver inflammation. Front. Immunol. 13, 1083780, doi: 10.3389/fimmu.2022.1083780.

33. Higashi, T., Friedman, S.L. & Hoshida, Y. (2017) Hepatic stellate cells as key target in liver fibrosis. Adv. Drug Deliv. Rev. 121, 27-42, doi: 10.1016/j.addr.2017.05.007.

34. Luedde, T., Kaplowitz, N. & Schwabe, R.F. (2014) Cell death and cell death responses in liver disease: mechanisms and clinical relevance. Gastroenterology. 147 (4), 765-783.e4, doi: 10.1053/j.gastro.2014.07.018.

35. Zhou, S., Gu, J., Liu, R., Wei, S., Wang, Q., Shen, H., Dai, Y., Zhou, H., Zhang, F. & Lu, L. (2018) Spermine Alleviates Acute Liver Injury by Inhibiting Liver-Resident Macrophage Pro-Inflammatory Response Through ATG5-Dependent Autophagy. Front. Immunol. 9, 948, doi: 10.3389/fimmu.2018.00948.

36. Kisseleva, T. & Brenner, D. (2021) Molecular and cellular mechanisms of liver fibrosis and its regression. Nat. Rev. Gastroenterol. Hepatol. 18 (3), 151-166, doi: 10.1038/s41575-020-00372-7.

37. Tsuchida, T. & Friedman, S.L. (2017) Mechanisms of hepatic stellate cell activation. Nat. Rev. Gastroenterol. Hepatol. 14 (7), 397-411, doi: 10.1038/nrgastro.2017.38.

38. Roehlen, N., Crouchet, E. & Baumert, T.F. (2020) Liver Fibrosis: Mechanistic Concepts and Therapeutic Perspectives. Cells. 9 (4), 875, doi: 10.3390/cells9040875.

39. Fabregat, I., Moreno-Càceres, J., Sánchez, A., Dooley, S., Dewidar, B., Giannelli, G., Ten Dijke, P. & IT-LIVER Consortium. (2016) TGF-β signalling and liver disease. FEBS J. 283 (12), 2219-2232, doi: 10.1111/febs.13665.

40. Shirato, T., Homma, T., Lee, J., Kurahashi, T. & Fujii, J. (2017) Oxidative stress caused by a SOD1 deficiency ameliorates thioacetamide-triggered cell death via CYP2E1 inhibition but stimulates liver steatosis. Arch. Toxicol. 91 (3), 1319-1333, doi: 10.1007/s00204-016-1785-9.

41. Wei, D.D., Wang, J.S., Duan, J.A. & Kong, L.Y. (2018) Metabolomic Assessment of Acute Cholestatic Injuries Induced by Thioacetamide and by Bile Duct Ligation, and the Protective Effects of Huang-Lian-Jie-Du-Decoction. Front. Pharmacol. 9, 458, doi: 10.3389/fphar.2018.00458.

42. Farghali, H., Canová, N.K. & Zakhari, S. (2015) Hepatoprotective properties of extensively studied medicinal plant active constituents: possible common mechanisms. Pharmaceutical biology. 53 (6), 781-791, doi: 10.3109/13880209.2014.950387.

43. Polukhina, A.V., Vinnitskaya, E.V., Sandler, Yu.G. & Khaimenova T.Yu. (2017) [Ademetionine in the treatment of non-alcoholic fatty liver disease]. Meditsinskiy Sovet = Medical Council. (15), 104-111, doi: 10.21518/2079-701X-2017-15-104-111. (In Russian).

44. Vergani, L., Baldini, F., Khalil, M., Voci, A., Putignano, P. & Miraglia, N. (2020) New Perspectives of S-Adenosylmethionine (SAMe) Applications to Attenuate Fatty Acid-Induced Steatosis and Oxidative Stress in Hepatic and Endothelial Cells. Molecules (Basel, Switzerland). 25 (18), 4237, doi: 10.3390/molecules25184237.

45. Li, H., Liu, N.N. & Peng, Z.G. (2020) Effect of bicyclol on blood biomarkers of NAFLD: a systematic review and meta-analysis. BMJ open. 10 (12), e039700, doi: 10.1136/bmjopen-2020-039700.

46. Dludla, P.V., Nkambule, B.B., Mazibuko-Mbeje, S.E., Nyambuya, T.M., Marcheggiani, F., Cirilli, I., Ziqubu, K., Shabalala, S.C., Johnson, R., Louw, J., Damiani, E. & Tiano, L. (2020) N-Acetyl Cysteine Targets Hepatic Lipid Accumulation to Curb Oxidative Stress and Inflammation in NAFLD: A Comprehensive Analysis of the Literature. Antioxidants (Basel, Switzerland). 9 (12), 1283, doi: 10.3390/antiox9121283.

47. Karedath, J., Javed, H., Ahsan Talpur, F., Lal, B., Kumari, A., Kivan, H., Anirudh Chunchu, V. & Hirani, S. (2022) Effect of Vitamin E on Clinical Outcomes in Patients With Non-alcoholic Fatty Liver Disease: A Meta-Analysis. Cureus. 14 (12), e32764, doi: 10.7759/cureus.32764.

48. Myshkin, V.A. & Enikeev, D.A. (2014) [Antioxidants of pyrimidine structure as means of correcting lipid peroxidation induced by a toxic factor]. Meditsinskiy vestnik Bashkortostana = Bashkortostan Medical Journal. 9 (5), 143-146. (In Russian).

49. Zuñiga-Aguilar, E. & Ramírez-Fernández, O. (2022) Fibrosis and hepatic regeneration mechanism. Transl. Gastroenterol. Hepatol. 7, 9, doi: 10.21037/tgh.2020.02.21.

50. Radun, R. & Trauner, M. (2021) Role of FXR in Bile Acid and Metabolic Homeostasis in NASH: Pathogenetic Concepts and Therapeutic Opportunities. Semin. Liver Dis. 41 (4), 461-475, doi: 10.1055/s-0041-1731707.

51. Ebaid, H., Bashandy, S.A., Morsy, F.A., Al-Tamimi, J., Hassan, I. & Alhazza, I.M. (2023) Protective effect of gallic acid against thioacetamide-induced metabolic dysfunction of lipids in hepatic and renal toxicity. J. King Saud Univ. Sci. 35 (3), 102531, doi: 10.1016/j.jksus.2022.102531.

52. Wu, J., Gong, L., Li, Y., Qu, J., Yang, Y., Wu, R., Fan, G., Ding, M., Xie, K., Li, F. & Li, X. (2024) Tao-Hong-Si-Wu-Tang improves thioacetamide-induced liver fibrosis by reversing ACSL4-mediated lipid accumulation and promoting mitophagy. J. Ethnopharmacol. 333, 118456, doi: 10.1016/j.jep.2024.118456.

53. Aldini, G., Altomare, A., Baron, G., Vistoli, G., Carini, M., Borsani, L. & Sergio, F. (2018) N-Acetylcysteine as an antioxidant and disulphide breaking agent: the reasons why. Free Radic. Res. 52 (7), 751-762, doi: 10.1080/10715762.2018.1468564.

54. Zhitkovich, A. (2019) N-Acetylcysteine: Antioxidant, Aldehyde Scavenger, and More. Chem. Res. Toxicol. 32 (7), 1318-1319, doi: 10.1021/acs.chemrestox.9b00152.

55. Myshkin, V.A. & Enikeyev, D.A. (2014) Hepatoprotection against chemical influence: comparative effects of 5-hydroxy-6-methyluracil (oxymethyluracil), complex compound «oxymethyluracil + sodium succinate» and silymarine. Arch. Euromedica. 4 (1), 45-49.

56. Khazimullina, Y.Z., Gimadieva, A.R., Khairullina, V.R., Kudoyarov, E.R., Karimov, D.O. & Mustafin, A.G. (2025) Synthesis and Study of the Hepatoprotective Activity of New Uracil Derivatives. Russ. J. Bioorg. Chem. 51, 117-127, doi: 10.1134/S1068162025010157.

57. Waters, N.J., Waterfield, C.J., Farrant, R.D., Holmes, E. & Nicholson, J.K. (2005) Metabonomic deconvolution of embedded toxicity: application to thioacetamide hepato- and nephrotoxicity. Chem. Res. Toxicol. 18 (4), 639-654, doi: 10.1021/tx049869b.

58. Provost, J.P., Hanton, G. & Net, J.L. (2003) Plasma triglycerides: an overlooked biomarker of hepatotoxicity in the rat. Comp. Clin. Pathol. 12 (2), 95-101.

59. Horn, P. & Tacke, F. (2024) Metabolic reprogramming in liver fibrosis. Cell Metab. 36 (7), 1439-1455, doi: 10.1016/j.cmet.2024.05.003.

60. Delgado, M.E., Cárdenas, B.I., Farran, N. & Fernandez, M. (2021) Metabolic Reprogramming of Liver Fibrosis. Cells. 10 (12), 3604, doi: 10.3390/cells10123604.

61. Zhang, D., Shi, C., Wang, Y., Guo, J. & Gong, Z. (2024) Metabolic Dysregulation and Metabolite Imbalances in Acute-on-chronic Liver Failure: Impact on Immune Status. J. Clin. Transl. Hepatol. 12 (10), 865-877, doi: 10.14218/JCTH.2024.00203.

62. Zhang, I.W., Curto, A., López-Vicario, C., Casulleras, M., Duran-Güell, M., Flores-Costa, R., Colsch, B., Aguilar, F., Aransay, A.M., Lozano, J.J., Hernández-Tejero, M., Toapanta, D., Fernández, J., Arroyo, V. & Clària, J. (2022) Mitochondrial dysfunction governs immunometabolism in leukocytes of patients with acute-on-chronic liver failure. J. Hepatol. 76 (1), 93-106, doi: 10.1016/j.jhep.2021.08.009.

63. Saxena, N. & Chandra, N.C. (2020) Cholesterol: A Prelate in Cell Nucleus and its Serendipity. Curr. Mol. Med. 20 (9), 692-707, doi: 10.2174/1566524020666200413112030.

64. Shi, L., Chen, H., Zhang, Y., An, D., Qin, M., Yu, W., Wen, B., He, D., Hao, H. & Xiong, J. (2025) SLC13A2 promotes hepatocyte metabolic remodeling and liver regeneration by enhancing de novo cholesterol biosynthesis. EMBO J. 44 (5), 1442-1463, doi: 10.1038/s44318-025-00362-y.