Effect of long-term immunosuppressive therapy on native rat liver morphology and hepatocyte- apoptosis

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.

Keywords: Apoptosis; Immunosuppressive drugs; Liver; Morphology.