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


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Pekmezekmek A. B. , BİNOKAY U. S. , SEÇİLMİŞ M. A. , KUMCU E. , Simsek E., AKILLIOĞLU K. , et al.

DRUG AND CHEMICAL TOXICOLOGY, cilt.38, ss.254-265, 2015 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Cilt numarası: 38 Konu: 3
  • Basım Tarihi: 2015
  • Doi Numarası: 10.3109/01480545.2014.947423
  • Dergi Adı: DRUG AND CHEMICAL TOXICOLOGY
  • Sayfa Sayısı: ss.254-265

Özet

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 mg/L, an EC50 of 0.006 mg/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 mg/L, 0.868 mg/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 mg/L and 0.1 mg/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.

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 mg/L, an EC50 of 0.006 mg/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 mg/
L, 0.868 mg/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 mg/L and 0.1 mg/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.