title: 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.
authors.affiliation: Department of Anatomy, Medical Faculty, Selcuk University, Konya, Turkey. Electronic address: nunver2003@yahoo.com.
authors.forename: Nadire
authors.initials: N
authors.lastname: Unver Dogan
authors.affiliation: Department of Anatomy, Medical Faculty, Selcuk University, Konya, Turkey.
authors.forename: Ismihan Ilknur
authors.initials: II
authors.lastname: Uysal
authors.affiliation: Department of Anatomy, Medical Faculty, Selcuk University, Konya, Turkey.
authors.forename: Zeliha
authors.initials: Z
authors.lastname: Fazliogullari
authors.affiliation: Department of Anatomy, Medical Faculty, Selcuk University, Konya, Turkey.
authors.forename: Ahmet Kagan
authors.initials: AK
authors.lastname: Karabulut
authors.affiliation: Department of Medical Genetics, Medical Faculty, Selcuk University, Konya, Turkey.
authors.forename: Hasan
authors.initials: H
authors.lastname: Acar
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000209:etiology* / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016572:Cyclosporine / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D046149:Embryo Culture Techniques; D004622:Embryo, Mammalian / Q000002:abnormalities / Q000187:drug effects*; D005260:Female; D005865:Gestational Age; D006406:Hematoma / Q000139:chemically induced; D006801:Humans; D007166:Immunosuppressive Agents / Q000633:toxicity*; D009436:Neural Tube Defects / Q000139:chemically induced; D011239:Prednisolone / Q000633:toxicity*; D011247:Pregnancy; D017208:Rats, Wistar; D018570:Risk Assessment; D016559:Tacrolimus / Q000633:toxicity*; D013723:Teratogens / Q000633:toxicity*; D018675:Toxicity Tests
chemical_list: D007166:Immunosuppressive Agents; D013723:Teratogens; D016572:Cyclosporine; D011239:Prednisolone; D016559:Tacrolimus
keywords: Apoptosis; Cyclosporine A; In vitro embryo culture; Prednisolone; Tacrolimus