title: Evaluating the Teratogenicity of Ritodrine and Nifedipine using a Frog Embryo Teratogenesis assay (FETAX).
abstract: The Frog Embryo Teratogenesis Assay-Xenopus (FETAX) was used to assess the teratogenic potential of two tocolytics. Embryos of the South African clawed frog, Xenopus laevis, were exposed to ritodrine or nifedipine. Exposure media were changed and monitored at 24-hour intervals. The 96-hour LC50 (Lethal concentration), the 96-hour EC50 (Malformation), and the No Observable Adverse Effect Concentrations (NOAEC) and the Lowest Observable Adverse Effect Concentration (LOAEC) for mortality, malformation and length were determined for each drug. Nifedipine was determined to be the more toxic and teratogenic than ritodrine, with a LC50 of 0.606 µg/L, an EC50 of 0.006 µg/L, and a teratogenicity Index (TI) value (LC50/EC50) of 101. On the other hand, the LC50 of ritodrine was 28.571 mg/L. In addition; the LC50, EC50 and TI values for nifedipine in the 5 mg/L ritodrine + nifedipine combination group were determined as 1.050 µg/L, 0.868 µg/L and 1.5 respectively. For ritodrine, the NOAEC and LOAEC values were determined as 2 mg/L and 4 mg/L, respectively. For the nifedipine and the ritodrine + nifedipine groups; while the LOAEC values of these groups were 0.0001 µg/L and 0.1 µg/L, respectively. NOAEC value couldn't be determined. Our results demonstrated that nifedipine administration was associated with higher levels of teratogenic and toxic effects. However, the ritodrine + nifedipine combination form reduced the toxic and teratogenic effects of nifedipine on Xenopus embryos. Further studies should be conducted in order to investigate the optimal combination concentrations of these substances for the treatment of preterm labor.
authors.affiliation: Department of Physiology .
authors.forename: Ayper
authors.initials: A
authors.lastname: Boğa Pekmezekmek
authors.forename: Uğur Seçil
authors.initials: US
authors.lastname: Binokay
authors.forename: Mehmet Ata
authors.initials: MA
authors.lastname: Seçilmiş
authors.forename: Eda
authors.initials: E
authors.lastname: Kumcu
authors.forename: Erhan
authors.initials: E
authors.lastname: Şimşek
authors.forename: Kübra
authors.initials: K
authors.lastname: Akillioğlu
authors.forename: Yaşar
authors.initials: Y
authors.lastname: Sertdemir
authors.forename: Besim
authors.initials: B
authors.lastname: Özaykan
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000818:Animals; D001681:Biological Assay; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004625:Embryo, Nonmammalian / Q000002:abnormalities / Q000187:drug effects*; D007928:Lethal Dose 50; D009543:Nifedipine / Q000633:toxicity*; D019055:No-Observed-Adverse-Effect Level; D018570:Risk Assessment; D012312:Ritodrine / Q000633:toxicity*; D064793:Teratogenesis; D013997:Time Factors; D046509:Tissue Culture Techniques; D015149:Tocolytic Agents / Q000633:toxicity*; D018675:Toxicity Tests / Q000379:methods*; D014982:Xenopus laevis / Q000196:embryology
chemical_list: D015149:Tocolytic Agents; D012312:Ritodrine; D009543:Nifedipine
keywords: FETAX; Xenopus; nifedipine; preterm labor; ritodrine