title: Investigation of developmental toxicity and teratogenicity of antiemetics on rat embryos cultured in vitro.
abstract: 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 μg/ml), metoclopramide (10-50 μg/ml) and trimethobenzamide HCl (25-100 μg/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.
authors.affiliation: Department of Anatomy, Selcuklu Medical Faculty, Selcuk University, Konya, Turkey.
authors.forename: Z
authors.initials: Z
authors.lastname: Fazliogullari
authors.forename: A K
authors.initials: AK
authors.lastname: Karabulut
authors.forename: I I
authors.initials: II
authors.lastname: Uysal
authors.forename: N
authors.initials: N
authors.lastname: Unver Dogan
authors.forename: H
authors.initials: H
authors.lastname: Acar
mesh_terms: D000818:Animals; D000932:Antiemetics / Q000633:toxicity*; D001549:Benzamides / Q000633:toxicity*; D004111:Dimenhydrinate / Q000633:toxicity*; D046149:Embryo Culture Techniques; D004622:Embryo, Mammalian / Q000187:drug effects*; D047108:Embryonic Development / Q000187:drug effects*; D008787:Metoclopramide / Q000633:toxicity*; D009152:Mutagenicity Tests; D051381:Rats
chemical_list: D000932:Antiemetics; D001549:Benzamides; D004111:Dimenhydrinate; D008787:Metoclopramide; C100146:trimethobenzamide