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.

• FETAX
• nifedipine
• preterm labor
• ritodrine
• Xenopus

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

This work was supported by the scientific Research Office of the Çukurova University (I.U BAP). (Project No: TF2011BAP39).