ORIGINAL ARTICLE
The effect of immunosuppressive drugs based on calcineurin inhibitors on cell apoptosis and junctions between epithelial cells of rat’s jejunum
1
Department of Physiology, Pomeranian Medical University, Szczecin, Poland
2
Department of Histology and Embryology, Pomeranian Medical University, Szczecin, Poland
3
Clinic of Nephrology, Transplantology, and Internal Medicine, Pomeranian Medical University, Szczecin, Poland
4
Department of Gastroenterological Surgery and Transplantology, National Medical Institute, Ministry of Interior Affairs and Administration, Warsaw, Poland
Submission date: 2025-07-07
Acceptance date: 2025-08-04
Online publication date: 2026-09-18
Corresponding author
Kamila D. Misiakiewicz-Has
Department of Histology and Embryology, Pomeranian Medical University, 70-111 Szczecin, Poland
Department of Histology and Embryology, Pomeranian Medical University, 70-111 Szczecin, Poland
KEYWORDS
TOPICS
ABSTRACT
Introduction:
Long-term immunosuppressive therapy in organ recipients reduces the frequency and severity of graft rejection. However, it can also produce various side effects. Clinical evidence indicates that immunosuppressive drugs can have deleterious effects on the structure and function of the gastrointestinal epithelium, making it more susceptible to infectin, inflammation, and damage. It has also been documented that calcineurin inhibitors such as cyclosporine A (CsA) and tacrolimus (TAC) can have several effects on the morphology of various tissues.
Aim of the research:
The aim of the study was to evaluate the effects of chronic treatment of adult male rats with a three-drug regimen based on calcineurin inhibitors (CNIs) – cyclosporine A and tacrolimus in combination with rapamycin and glucocorticoid – on the morphology and function of the mucosal epithelium of the jejunum.
Material and methods:
Paraffin-embedded jejunum samples from 14-week-old male rats were analysed. The rats received immunosuppressive regimens based on calcineurin inhibitors with rapamycin and prednisone for 6 months. Histological (H-E) and immunohistochemical staining (annexin V, occludin, E-cadherin, vinculin) were performed. Digital image and histomorphometric analyses were conducted. The results underwent statistical evaluation using appropriate parametric and non-parametric tests.
Results and conclusions:
After 6 months of treatment with calcineurin inhibitors, a reduction in epithelial cell height was observed, along with increased apoptosis of cells in the apical surface of the jejunal villi, as well as changes in the immunoexpression levels of intercellular tight and adhesion junction proteins. This effect was more pronounced in the TRG group of rats.
Long-term immunosuppressive therapy in organ recipients reduces the frequency and severity of graft rejection. However, it can also produce various side effects. Clinical evidence indicates that immunosuppressive drugs can have deleterious effects on the structure and function of the gastrointestinal epithelium, making it more susceptible to infectin, inflammation, and damage. It has also been documented that calcineurin inhibitors such as cyclosporine A (CsA) and tacrolimus (TAC) can have several effects on the morphology of various tissues.
Aim of the research:
The aim of the study was to evaluate the effects of chronic treatment of adult male rats with a three-drug regimen based on calcineurin inhibitors (CNIs) – cyclosporine A and tacrolimus in combination with rapamycin and glucocorticoid – on the morphology and function of the mucosal epithelium of the jejunum.
Material and methods:
Paraffin-embedded jejunum samples from 14-week-old male rats were analysed. The rats received immunosuppressive regimens based on calcineurin inhibitors with rapamycin and prednisone for 6 months. Histological (H-E) and immunohistochemical staining (annexin V, occludin, E-cadherin, vinculin) were performed. Digital image and histomorphometric analyses were conducted. The results underwent statistical evaluation using appropriate parametric and non-parametric tests.
Results and conclusions:
After 6 months of treatment with calcineurin inhibitors, a reduction in epithelial cell height was observed, along with increased apoptosis of cells in the apical surface of the jejunal villi, as well as changes in the immunoexpression levels of intercellular tight and adhesion junction proteins. This effect was more pronounced in the TRG group of rats.
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| ISSN: | 1899-1874 |
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