Immunosuppressive treatment affects morphology and apoptotic intensity of the liver in pregnant Wistar rats

Introduction
Immunosuppressive drugs are crucial for patients who have undergone transplantation. These medicines prolong proper functioning of the transplanted organ, but, on the other hand, they lead to various disorders, including pathological alterations within native organs and apoptosis. The aim of our study was to investigate the influence of immunosuppressive drugs on morphology, physiology and hepatocyte apoptosis in the liver of pregnant female Wistar rats.

Material and methods
The study was conducted on 32 female rats exposed to immunosuppressive drugs before (2 weeks) and during pregnancy (3 weeks). The regimens included drugs commonly used in therapy following kidney transplantation (cyclosporine A, mycophenolate mofetil, prednisone, tacrolimus and everolimus).

Results
We observed a decreased liver weight in all treated dams in comparison to the control rats. No statistically significant differences among all examined groups were found regarding the concentration of either alanine or aspartate aminotransferase. The most pronounced apoptosis and the most severe morphological abnormalities were found in rats treated with cyclosporine A, prednisone and everolimus; but moderate changes were visible in other treatment groups. The alterations that we observed included dilated sinusoids, inflammation foci, the disappearance of boundaries between hepatocytes, ruptured blood vessels, degradation of cytoplasm, and hemosiderosis.

Conclusions
It seems possible that the alterations seen here are due to the early stage of liver damage, and that the biochemical parameters of the liver were not affected yet. Immunosuppressive therapy during pregnancy disturbs the physiology of the liver, and causes morphological changes in this organ.