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Effect of long-term immunosuppressive therapy on native rat liver morphology and hepatocyte- apoptosis
Aleksandra Wilk1, Dagmara Szypulska-Koziarska1, Karolina Kędzierska-Kapuza2
1Department of Histology and Embryology, Pomeranian Medical University, Szczecin, Poland.
Abstract:
A negative result of therapy based on immunosuppressive drugs is its leading to pathological alterations in the organ, including liver. Use of immunosuppressive medication may also lead to organized and genetically controlled cell death - apoptosis. The aim of this study was to examine histopathological changes in the livers of rats treated with immunosuppressive drugs, and also to determine the effects of different groups of immunosuppressive drugs on apoptosis activity in the hepatocytes of rat livers. The study was conducted on archival material obtained from Department of Nephrology, Transplantology and Internal Medicine of the Independent Public Clinical Hospital No. 2 at the Pomeranian Medical University in Szczecin, Poland. Statistical comparison of the treatment groups showed that all groups with rapamycin (sirolimus)-based regimens: Tacrolimus, Rapamycin, Glucocorticosteroid (TRG); Cyclosporine, Rapamycin, Glucocorticosteroid (CRG); Mycophenolate, Rapamycin, Glucocorticosteroid (MRG) and additionally Cyclosporine, Mycophenolate, Glucocorticosteroid (CMG) exhibited significantly more pronounced apoptosis than the control group, with p < 0.01, p < 0.05, p < 0.01 and p < 0.01, respectively. Furthermore, in the TRG group, over 90% of apoptotic hepatocytes were seen in the examined classic lobules. Additionally, every liver from treatment group was pathologically altered, including dilated sinusoids, pyknotic nuclei, swollen walls of the vessels. Long-lasting immunosuppressive treatment affects the liver both in terms of histological changes within the structure of the liver and in terms of the percentage of apoptotic hepatocytes. The following study seems to be very innovating due to the duration of the experiment and used drugs-protocols, since they reflect human treatment.
Insights
Immunosuppressive drugs cause significant liver damage and increased apoptosis in hepatocytes. All tested drug regimens, particularly those including rapamycin (sirolimus), led to pronounced pathological changes and cell death in rat livers.
Area of Science:
- Hepatology
- Immunology
- Toxicology
Background:
- Immunosuppressive drugs are crucial for preventing organ transplant rejection.
- These medications can cause significant side effects, including liver damage.
- Apoptosis, or programmed cell death, is a known consequence of immunosuppression.
Purpose of the Study:
- To investigate histopathological changes in rat livers following immunosuppressive drug treatment.
- To assess the impact of different immunosuppressive drug regimens on hepatocyte apoptosis.
- To evaluate the effects of rapamycin (sirolimus)-based protocols on liver tissue.
Main Methods:
- Archival liver tissue samples from rats treated with various immunosuppressive drug regimens were analyzed.
- Histopathological examination focused on identifying pathological alterations and apoptosis.
- Statistical comparisons were made between treatment groups and a control group.
Main Results:
- All immunosuppressive drug regimens, especially those including rapamycin (sirolimus), significantly increased hepatocyte apoptosis compared to controls.
- The Tacrolimus, Rapamycin, Glucocorticosteroid (TRG) group showed over 90% apoptotic hepatocytes.
- Pathological changes, including dilated sinusoids and pyknotic nuclei, were observed in all treated groups.
Conclusions:
- Long-term immunosuppressive treatment induces significant histological changes in the liver.
- Immunosuppressive drug protocols, particularly rapamycin-based ones, elevate hepatocyte apoptosis rates.
- These findings highlight the critical impact of immunosuppression on liver health and cellular integrity.
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