Assessment of indicators of myocardial fibrosis in experimental type 2 diabetes mellitus and with administration of L-arginine and N-acetyl-L-cysteine

Authors

DOI:

https://doi.org/10.26641/1997-9665.2026.2.27-34

Keywords:

type 2 diabetes mellitus, cardiomyopathy, myocardial fibrosis, collagen type 1, L-arginine, N-acetyl-L-cysteine, morphometry, rats

Abstract

Background. The study is devoted to diffuse myocardial fibrosis in type 2 diabetes mellitus and the possibilities of its correction with the help of L-arginine and N-acetylcysteine. The work evaluates the potential of these compounds to modify already formed structural changes in the heart and the possibility of preventing further damage in conditions of insulin resistance and metabolic overload. Aim. To evaluate the morphological effects of L-arginine and N-acetyl-L-cysteine on interstitial and perivascular components of myocardial fibrosis in experimental type 2 diabetes mellitus (T2DM) in Wistar rats. Methods and Results. The study was conducted on 42 Wistar rats (18-20 months old). T2DM was induced by a high-fat diet combined with streptozotocin (30 mg/kg). The animals were divided into groups: control, T2DM without correction, T2DM treated with L-arginine (1.5 g/kg), and T2DM treated with N-acetyl-L-cysteine (1.5 g/kg) for 2 weeks. Masson's trichrome staining and immunofluorescence analysis for collagen type 1 were performed. T2DM was found to increase interstitial fibrosis by 3.94 times and perivascular fibrosis by 2.24 times compared to the control group. The content of collagen type 1 increased by 492 %. L-arginine administration led to a further increase in interstitial fibrosis (1.21 times) and collagen type 1 content (by 18 %). N-acetyl-L-cysteine treatment promoted a 0.74-fold reduction in interstitial fibrosis but was accompanied by a 44 % increase in collagen type 1 expression. Conclusions. Experimental T2DM forms pronounced diffuse myocardial fibrosis dominated by the interstitial component and collagen type 1 accumulation. L-arginine does not exhibit a fibroprotective effect in this model. N-acetyl-L-cysteine partially reduces interstitial fibrosis but does not prevent the pathological expression of collagen type 1.

References

  1. Zhu T, Ye Z, Song J, Zhang J, Zhao Y, Xu F, Wang J, Huang X, Gao B, Li F. Effect of extracellular matrix stiffness on efficacy of Dapagliflozin for diabetic cardiomyopathy. Cardiovasc Diabetol. 2024;23(1):273. doi: 10.1186/s12933-024-02369-x.
  2. Al Ali L, Meijers WC, Beldhuis IE, Groot HE, Lipsic E, van Veldhuisen DJ, Voors AA, van der Horst ICC, de Boer RA, van der Harst P. Association of fibrotic markers with diastolic function after STEMI. Sci Rep. 2024;14(1):19122. doi: 10.1038/s41598-024-69926-y.
  3. van Ham WB, Kessler EL, Oerlemans MIFJ, Handoko ML, Sluijter JPG, van Veen TAB, den Ruijter HM, de Jager SCA. Clinical Phenotypes of Heart Failure With Preserved Ejection Fraction to Select Preclinical Animal Models. JACC Basic Transl Sci. 2022;7(8):844-57. doi: 10.1016/j.jacbts.2021.12.009.
  4. Radovits T, Korkmaz S, Mátyás C, Oláh A, Németh BT, Páli S, Hirschberg K, Zubarevich A, Gwanmesia PN, Li S, Loganathan S, Barnucz E, Merkely B, Szabó G. An altered pattern of myocardial histopathological and molecular changes underlies the different characteristics of type-1 and type-2 diabetic cardiac dysfunction. J Diabetes Res. 2015;2015:728741. doi: 10.1155/2015/728741.
  5. Chen K, Wang S. New insights into FGF21 alleviates diabetic cardiomyopathy by suppressing ferroptosis: a commentary. Cardiovasc Diabetol. 2024;23(1):424. doi: 10.1186/s12933-024-02519-1.
  6. European Parliament, Council of the European Union. 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;L276:33-79.
  7. Ukraine. Law No. 3447-IV "On the Protection of Animals from Cruelty". Vidomosti Verkhovnoi Rady Ukrainy. 2006;27:230. Ukrainian.
  8. Kolesnyk YM, Isachenko MI. Modeling insulin resistance in Wistar rats induced by a combined high-fat diet as a predictor of type 2 diabetes (experimental phase 1 study). Pathologia. 2025;22(1):5-11. doi: 10.14739/2310-1237.2025.1.314277.
  9. Islam MA, Kumar S. Masson's Trichrome Staining Technique to Evaluate Tissue Fibrosis. Methods Mol Biol. 2026;2983:91-100. doi: 10.1007/978-1-0716-4901-5_9.
  10. Ruifrok AC, Johnston DA. Quantification of histochemical staining by color deconvolution. Anal Quant Cytol Histol. 2001 Aug;23(4):291-9. PMID: 11531144.
  11. Santa Cruz Biotechnology. Immunofluorescence Cell Staining [Internet]. Dallas (TX): Santa Cruz Biotechnology. Available from: https://www.scbt.com/resources/protocols/immunofluorescence-cell-staining.
  12. Chatzi A, Doody O. The one-way ANOVA test explained. Nurse Res. 2023;31(3):8-14. doi: 10.7748/nr.2023.e1885.
  13. Li Y, Xian H, Xu Y, Li W, Guo J, Wan K, Wang J, Xu Z, Zhang Q, Han Y, Sun J, Chen Y. The impact of type 2 diabetes mellitus on the clinical profile, myocardial fibrosis, and prognosis in non-ischemic dilated cardiomyopathy: a prospective cohort study. Cardiovasc Diabetol. 2024;23(1):48. doi: 10.1186/s12933-024-02134-0.
  14. Pan KL, Hsu YC, Chang ST, Chung CM, Lin CL. The Role of Cardiac Fibrosis in Diabetic Cardiomyopathy: From Pathophysiology to Clinical Diagnostic Tools. Int J Mol Sci. 2023;24(10):8604. doi: 10.3390/ijms24108604.
  15. Tudurachi BS, Anghel L, Tudurachi A, Sascău RA, Zanfirescu RL, Stătescu C. Unraveling the Cardiac Matrix: From Diabetes to Heart Failure, Exploring Pathways and Potential Medications. Biomedicines. 2024;12(6):1314. doi: 10.3390/biomedicines12061314.
  16. Cheng Y, Wang Y, Yin R, Xu Y, Zhang L, Zhang Y, Yang L, Zhao D. Central role of cardiac fibroblasts in myocardial fibrosis of diabetic cardiomyopathy. Front Endocrinol (Lausanne). 2023;14:1162754. doi: 10.3389/fendo.2023.1162754.
  17. Thakur MR, Tupe RS. l-Arginine in diabetic cardiomyopathy: Mechanistic insights into RAGE-NF-κB-SREBP1 signaling. Biochem Biophys Res Commun. 2026;797:153212. doi: 10.1016/j.bbrc.2025.153212.
  18. Wang R, Zhang X, Ye H, Yang X, Zhao Y, Wu L, Liu H, Wen Y, Wang J, Wang Y, Yu M, Ma C, Wang L. Fibroblast growth factor 21 improves diabetic cardiomyopathy by inhibiting ferroptosis via ferritin pathway. Cardiovasc Diabetol. 2024;23(1):394. doi: 10.1186/s12933-024-02469-8.
  19. Liu H, Yan W, Ma C, Zhang K, Li K, Jin R, Xu H, Xu R, Tong J, Yang Z, Guo Y. Early detection of cardiac fibrosis in diabetic mice by targeting myocardiopathy and matrix metalloproteinase 2. Acta Biomater. 2024;176:367-78. doi: 10.1016/j.actbio.2024.01.017.

Published

2026-05-29

How to Cite

Isachenko , M. (2026). Assessment of indicators of myocardial fibrosis in experimental type 2 diabetes mellitus and with administration of L-arginine and N-acetyl-L-cysteine. Морфологія / Morphologia / Morfologìâ, 20(2), 27–34. https://doi.org/10.26641/1997-9665.2026.2.27-34

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