Morphological characteristics and assessment of histological changes in the rats' liver under modeling type 2 diabetes and its correction by N-stearoylethanolamine

Authors

DOI:

https://doi.org/10.26641/1997-9665.2025.4.55-63

Keywords:

type 2 diabetes mellitus; experimental model; rats; histological changes in the liver; N-stearoylethanolamine; pharmacological correction.

Abstract

Background. The problem of diabetes mellitus, in particular type 2 diabetes mellitus (T2DM), is becoming global worldwide, which determines the relevance of prevention, diagnosis and treatment of one of its most common complications - metabolic dysfunction-associated steatotic liver disease (MASLD). The ability of the liver to reverse changes in DM2Т determines the need to search, develop and implement in clinical practice new means of pharmacological correction of MASLD. Objective. Morphological characterization and development of an objective approach for comparative assessment and unification of histological changes in the liver of rats in modeling T2DM and its correction with N-stearoylethanolamine (NSE). Methods. A model of T2DM was reproduced in Sprague-Dawley rats (n=41) maintained on a high-fat diet (HFD) for a long time (6 months). Based on the results of liver histological examination, the effects of therapeutic action of NSE (per os, at a dose of 50 mg/kg, for 2 weeks after confirmation of the development of T2DM; scheme 1) and its preventive action (per os, at a dose of 50 mg/kg, 10 days each month; scheme 2) were studied. Results. Morphological studies of the liver of rats in the simulation of T2DM revealed changes characteristic of MASLD, which were determined by such histological patterns as: disruption of the histostructure of the organ; impaired blood circulation in the liver; dystrophic changes in hepatocytes, primarily steatosis; necrosis/apoptosis of hepatocytes and inflammatory changes in the liver; fibrosis, as well as compensatory and adaptive changes in hepatocytes. Based on the results obtained, a standardized unified protocol for histological examination of the liver of rats with T2DM and criteria for assessing the detected changes according to 3 assessment categories using a scoring system from «0» to «3» were developed. Conclusion. The implementation of the developed system for assessing histological changes in the liver during the modeling of T2DM and its correction with NSE allowed for a comparative assessment of the effects of NSE in the experiment with different schemes of its application in rats. It was found that the use of NSE according to scheme 2 compared to scheme 1 significantly (p<0.05) reduces the manifestations of such histological changes as violations of the histostructure of the organ and its blood circulation, dystrophic changes in hepatocytes, primarily steatosis, necrosis/apoptosis and inflammatory changes, as well as fibrosis. At the same time, the effect of NSE significantly (p<0.05) increases the manifestations of compensatory-adaptive restructuring of hepatocytes in the form of their hypertrophy.

References

  1. Federation, International Diabetes. IDF Diabetes Atlas 11th Edition - 2025. [Internet] Global-Factsheet. Available from: https://diabetesatlas.org/resources/idf-diabetes-atlas-2025/
  2. Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016;64(1):73-84. doi: 10.1002/hep.28431.
  3. Golabi P, Paik JM, AlQahtani S, Younossi Y, Tuncer G, Younossi ZM. Burden of non-alcoholic fatty liver disease in Asia, the Middle East and North Africa: Data from Global Burden of Disease 2009-2019. J Hepatol. 2021;75(4):795-809. doi: 10.1016/j.jhep.2021.05.022.
  4. Younossi ZM, Golabi P, Paik JM, Henry A, Van Dongen C, Henry L. The global epidemiology of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH): a systematic review. Hepatology. 2023;77(4):1335-47. doi: 10.1097/ HEP.0000000000000004.
  5. Chan WK, Chuah KH, Rajaram RB, Lim LL, Ratnasingam J, Vethakkan SR. Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): A State-of-the-Art Review. J Obes Metab Syndr. 2023;32(3):197-213. doi: 10.7570/ jomes23052.
  6. Lazarus JV, Newsome PN, Francque SM, Kanwal F, Terrault NA, Rinella ME. Reply: A multi-society Delphi consensus statement on new fatty liver disease nomenclature. Hepatology. 2024;79(3):E93-E94. doi: 10.1097/HEP.0000000000000696.
  7. Berdyshev AG, Kosiakova HV, Onopchenko OV, Panchuk RR, Stoika RS, Hula NM. N-Stearoylethanolamine suppresses the pro-inflammatory cytokines production by inhibition of NF-κB translocation. Prostaglandins Other Lipid Mediat. 2015;121(Pt A):91-6. doi: 10.1016/j.prostaglandins.2015.05.001.
  8. Onopchenko OV, Kosiakova GV, Oz M, Klimashevsky VM, Gula NM. N-stearoylethanolamine restores pancreas lipid composition in obesity-induced insulin resistant rats. Lipids. 2015;50(1):13-21. doi: 10.1007/s11745-014-3960-1.
  9. European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Stientific Purposes. Strasburg: Council of Europe. 1986;123:52. Available from: https://rm.coe.int/ 168007a67b.
  10. Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the Protection of Animals Used for Scientific Purposes. Off J Eur Union. 2010;53(L276):33–79.
  11. Zakon Ukrainy. Pro zakhyst tvaryn vid zhorstokogo povodzhennia [Law of Ukraine. On the protection of animals from cruelty]. Vidomosti Verkhovnoi Rady Ukrainy (VVR). 2006;27:230. Available from: http://zakon1.rada.gov.ua/laws/ show/3447-15.
  12. Ejima C, Kuroda H, Ishizaki S. A novel diet-induced murine model of steatohepatitis with fibrosis for screening and evaluation of drug candidates for nonalcoholic steatohepatitis. Physiol Rep. 2016;4(21):e13016. doi: 10.14814/phy2.13016.
  13. Zhong F, Zhou X, Xu J, Gao L. Rodent Models of Nonalcoholic Fatty Liver Disease. Digestion. 2020;101(5):522-35. doi: 10.1159/000501851.
  14. Wang H, Shen H, Seo W, Hwang S. Experimental models of fatty liver diseases: Status and appraisal. Hepatol Commun. 2023;7(7):e00200. doi: 10.1097/HC9.0000000000000200.
  15. Bagrij MM, Dibrova VF, editors. Metodyky` morfologichnyx doslidzhen: monografiya. [Methods of morphological research: monograph] Vinnycya: Nova Knyga; 2016. 328 p. Ukrainion.
  16. Brunt EM. Nonalcoholic Fatty Liver Disease: Pros and Cons of Histologic Systems of Evaluation. Int J Mol Sci. 2016;17(1):97. doi: 10.3390/ ijms17010097.
  17. Dezső K, Paku S, Juhász M-M, Kóbori L, Nagy P. Evolutionary view of liver pathology. Evol Applicat. 2024;17:e70059. doi: 10.1111/eva.70059.
  18. Goodman ZD. Grading and staging systems for inflammation and fibrosis in chronic liver diseases. J Hepatol. 2007;47(4):598-607. doi: 10.1016/ j.jhep.2007.07.006.
  19. Krishna M. Patterns of necrosis in liver disease. Clinical liver disease (Hoboken), 2017;10(2):53-6. doi: 10.1002/cld.653.
  20. Liang W, Menke AL, Driessen A, Koek GH, Lindeman JH, Stoop R, et al. Establishment of a general NAFLD scoring system for rodent models and comparison to human liver pathology. PLoS One. 2014;9(12):e115922. doi: 10.1371/journal.pone. 0115922.
  21. Yin X, Guo X, Liu Z, Wang J. Advances in the Diagnosis and Treatment of Non-Alcoholic Fatty Liver Disease. Int J Mol Sci. 2023;24(3):2844. doi: 10.3390/ijms24032844.

Published

2025-10-30

How to Cite

Luhovskyi , S., Kvitnitskaya-Ryzhova, T., Mykhalskiy , S., Klymenko , P., Malysheva , S., & Kosiakova , G. (2025). Morphological characteristics and assessment of histological changes in the rats’ liver under modeling type 2 diabetes and its correction by N-stearoylethanolamine. Морфологія / Morphologia / Morfologìâ, 19(4), 55–63. https://doi.org/10.26641/1997-9665.2025.4.55-63

Issue

Section

Статті