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.

Mortality and malformation effects of acute vanadium (V) exposure on the African clawed frog (Xenopus laevis) embryos

“…For instance, V was notably higher than Cu (TI = 8.8) and Zn (TI = 21) (Luo et al 1993 ) and higher than roundup which had a calculated TI of 3.4 (Bonfanti et al 2018 ). Nifidipine, a pharmaceutical agent, was determined to have a TI of 101 (Boğa Pekmezekmek et al 2015 ). During the interlaboratory validation studies of the FETAX method, the TI values of 5-fluorouracil (TI = 6.7–18.7), caffeine (TI = 1.8–3.4), isoniazid (TI = 4.1–72.8), and 6-aminonicotinaminde (TI = 241.6 620.0) were assessed for variability (Bantle et al 1994a , b ).…”

Teratogenicity and Teratogenic Factors

“…However, ritodrine+nifedipine combination had reduced the toxic and teratogenic effects of nifedipine alone on embryos. 41 Environmental teratogenic pollutants lead to severe birth defects but the underlying biological mechanisms of these developmental abnormalities remain unclear. A link has been discovered between an environmental stress response pathway and key developmental genes during craniofacial development in mice.…”