Evaluating the Teratogenicity of Ritodrine and Nifedipine using a Frog Embryo Teratogenesis assay (FETAX)

• Published in: Drug and chemical toxicology (New York, N.Y. 1978) N.Y. 1978), 2015-07, Vol.38 (3), p.254-265
• Main Authors: Boğa Pekmezekmek, Ayper, Binokay, Uğur Seçil, Seçilmiş, Mehmet Ata, Kumcu, Eda, Şimşek, Erhan, Akillioğlu, Kübra, Sertdemir, Yaşar, Özaykan, Besim
• Format: Article
• Language: English
• Subjects: Abnormalities, Drug-Induced - etiology; Animals; Biological Assay; Dose-Response Relationship, Drug; Drug Interactions; Embryo, Nonmammalian - abnormalities; Embryo, Nonmammalian - drug effects; FETAX; Lethal Dose 50; nifedipine; Nifedipine - toxicity; No-Observed-Adverse-Effect Level; preterm labor; Risk Assessment; ritodrine; Ritodrine - toxicity; Teratogenesis; Time Factors; Tissue Culture Techniques; Tocolytic Agents - toxicity; Toxicity Tests - methods; Xenopus; Xenopus laevis - embryology
• ISSN: 0148-0545; 1525-6014
• DOI: 10.3109/01480545.2014.947423

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 LC 50 (Lethal concentration), the 96-hour EC 50 (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 LC 50 of 0.606 µg/L, an EC 50 of 0.006 µg/L, and a teratogenicity Index (TI) value (LC 50 /EC 50 ) of 101. On the other hand, the LC 50 of ritodrine was 28.571 mg/L. In addition; the LC 50 , EC 50 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.