Prenatal Exposition to Different Immunosuppressive Protocols Results in Vacuolar Degeneration of Hepatocytes

Immunosuppressive drugs are essential for transplant recipients, since they prolong proper function of graft; however, they affect the morphology and function of organs, including liver. One commonly observed alteration in hepatocytes is vacuolar degeneration. Numerous medications are contraindicated in pregnancy and breastfeeding, mostly due to a lack of data concerning their advert effects. The aim of the current study was to compare the effects of prenatal exposition to different protocols of immunosuppressants on vacuolar degeneration in the hepatocytes of livers of rats. Thirty-two livers of rats with usage of digital analysis of the images were examined. Area, perimeter, axis length, eccentricity and circularity regarding vacuolar degeneration were analysed. The most prominent vacuolar degeneration in hepatocytes in the aspects of presence, area and perimeter was observed in rats exposed to tacrolimus, mycophenolate mofetil and glucocorticoids, and cyclosporine A, everolimus with glucocorticoids.This is the first study that demonstrates the results of the influence of multidrug immnunosuppression distributed in utero on the hepatic tissue of offspring.

Automated summary

Immunosuppressive drugs used for transplant recipients have both advantages in prolonging graft function and adverse effects on liver morphology and function. This study compared the effects of prenatal exposure to different immunosuppressants on vacuolar degeneration in rat livers. The results showed that tacrolimus, mycophenolate mofetil, glucocorticoids, cyclosporine A, and everolimus with glucocorticoids had the highest incidence and severity of vacuolar degeneration in hepatocytes. This study provides valuable insights into the influence of multidrug immunosuppression on hepatic tissue in offspring.