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    Investigation of Developmental Toxicity and Teratogenicity of Antiemetics on Rat Embryos Cultured In Vitro
    (WILEY, 2013) Fazliogullari, Z.; Karabulut, A. K.; Uysal, I. I.; Unver Dogan, N.; Acar, H.
    In this study, we aimed to investigate and compare the direct toxic and teratogenic effects of dimenhydrinate, metoclopramide and trimethobenzamide HCl, antiemetic drugs on embryonic growth and development in cultured rat embryos. Embryos were explanted on day 9.5 of gestation and cultured. Whole rat serum was used as a culture medium for the control group while different concentrations of dimenhydrinate (2.5-20 mu g/ml), metoclopramide (10-50 mu g/ml) and trimethobenzamide HCl (25-100 mu g/ml) were added to serum for the experimental groups. Effects of antiemetics on embryonic developmental parameters were compared, and embryos were evaluated for the presence of any malformations. Also, the total DNA was extracted from the cells to determine the fragmentation of nuclear DNA of embryonic cells. Compared with the control embryos, the antiemetics significantly decreased all growth and developmental parameters dose dependently. There was no difference regarding the fragmentation of nuclear DNA of the all used agents and controls. Amongst the agents, trimethobenzamide HCl was found to have more toxic and teratogenic potential, and metoclopramide appears to be the least toxic antiemetic and therefore could be more safely used and might be preferred for the treatment of nausea and vomiting in pregnancy.
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    Investigation of developmental toxicity and teratogenicity of macrolide antibiotics in cultured rat embryos
    (WILEY, 2008) Karabulut, A. K.; Uysal, I. I.; Acar, H.; Fazliogullari, Z.
    Macrolides are considered to be one of the safest anti-infective groups in clinical use, with severe adverse reactions being rare. However, there are limited data about their embryotoxicity and teratogenicity. We aimed to investigate and compare the effects of these agents on embryonic growth and development. Rat embryos were cultured in vitro for 48 h in rat serum. Whole rat serum was used as a culture medium for the control group while different concentrations of spiramycin and azithromycin (1.25-6.25 mu g/ml), and clarithromycin (2.5-30 mu g/ml) were added to rat serum for the experimental groups. Dose-dependent effects of macrolides on embryonic developmental parameters were compared using morphological methods. Embryos were evaluated for the presence of any malformations. After morphological examination of the embryos, total DNA was extracted from the cells using standard procedures to determine fragmentation of nuclear DNA of embryonic cells. When compared with the control embryos, the macrolides significantly decreased all growth and developmental parameters dose dependently. While clarithromycin was found to cause more developmental toxicity than spiramycin and azithromycin, azitromycin was determined to have more teratogenicity potential. Compared with controls, there was no difference regarding the fragmentation of nuclear DNA of all the agents used. According to these results, when the toxic and teratogenic potential of the used agents compared, because of the lower toxic and teratogenic effects observed with spiramycin, this agent may be preferred for parturients.