Investigation of developmental toxicity and teratogenicity of cyclosporine A, tacrolimus and their combinations with prednisolone

Abstract

In this study, it was aimed to investigate the toxic and teratogenic effects of cyclosporine A and tacrolimus and their combinations with prednisolone using an in vitro rat embryo culture technique. Cyclosporine A (4–40 μg/ml), tacrolimus (1–20 μg/ml) and combinations of these drugs with prednisolone (20 μg/ml) at different concentrations were tested. Cyclosporine A and its combination with prednisolone were determined to have toxic effects on embryonic growth after 10 μg/ml. When used alone, the lowest dose of tacrolimus had embryotoxic effects on the total morphological score and number of somites. It was determined that cyclosporine A caused hematoma at 4 μg/ml and higher doses, and tacrolimus especially at 20 μg/ml caused an open neural tube beside hematoma. It was observed that cyclosporine A at 40 μg/ml dose initiated apoptotic effects at a very low rate, prednisolone increased this effect, tacrolimus led to excessive apoptosis after 15 μg/ml, and this effect did not change with prednisolone supplement. We are of the opinion that the doses should be determined carefully when cyclosporine A and tacrolimus are required to be administered to pregnant women with prednisolone combination, as prednisolone increases the toxic effects of cyclosporine A, and increases teratogenic effects of tacrolimus.