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Teratogenic effects of carbamazepine on embryonic eye development in pregnant mice

Afshar, M. and Moallem, S.A. and Houshang Mohammadpour, A. and Shiravi, A. and Majid Jalalian, S. and Jafar Golalipour, M. (2010) Teratogenic effects of carbamazepine on embryonic eye development in pregnant mice. Cutaneous and Ocular Toxicology, 29 (1). pp. 10-15. ISSN 15569527 (ISSN)

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Abstract

Background: Carbamazepine is an antiepileptic drug used widely for the treatment of epileptic seizures and neuropathic pain. Several malformations in humans, mainly neural tube defects, have been reported as a consequence of its use during pregnancy. The association between maternal use of carbamazepine and congenital eye malformations is not very well understood. Objective: The purpose of this study was to examine this association after intraperitoneal injection of carbamazepine during the period of organogenesis in mice. Methods: Balb/c timed-pregnant mice were divided into 4 experimental and control groups. Two experimental groups received daily intraperitoneal injections of 15mg/kg (group I) or 30mg/kg (group II) of carbamazepine on gestational days 6 to 15. Two control groups received normal saline or Tween 20 (polysorbate 20). Dams underwent Cesarean section on gestational day 18 and embryos were harvested. External examination for eye malformations, routine histological processing of malformed fetuses to study eye morphology, and skeletal staining were performed. Results: The mean weight and crown-rump of the fetuses in both experimental groups were significantly reduced compared with those of the control groups. Various malformations were detected such as brachygnathia, calvarial deformity, vertebral deformity, short tail, and brachydactyly. Premature opening of one or both eyes with mild to severe exophthalmos occurred in the 2 experimental groups. Deformed lens, retinal folds with undeveloped layers, and corneal folds with absence of surface epithelium were detected in both experimental groups. Conclusions: This study, to the best of our knowledge, showed for the first time that intraperitoneal administration of carbamazepine at clinically comparable doses during organogenesis can induce several eye malformations in mice. The implication of these results needs to be considered when carbamazepine is administered during human pregnancy. © 2010 Informa UK Ltd.

Item Type: Article
Additional Information: Unmapped bibliographic data: LA - English [Field not mapped to EPrints] J2 - Cutaneous Ocul. Toxicol. [Field not mapped to EPrints] C2 - 19895254 [Field not mapped to EPrints] AD - Department of Anatomy, Birjand University of Medical Sciences, Birjand, Iran [Field not mapped to EPrints] AD - Department of Pharmacodynamics and Toxicology, Mashhad University of Medical Sciences, Mashhad, Iran [Field not mapped to EPrints] AD - Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran [Field not mapped to EPrints] AD - Medical Toxicology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran [Field not mapped to EPrints] AD - Department of Biology, Azad Islamic University of Damghan, Damghan, Iran [Field not mapped to EPrints] AD - Department of Histology and Embryology, Gorgan Congenital Malformations Research Center, Gorgan University of Medical Sciences, Gorgan, Iran [Field not mapped to EPrints] DB - Scopus [Field not mapped to EPrints]
Uncontrolled Keywords: Carbamazepine, Mice, Ocular malformations, Pregnancy, Teratogenicity, carbamazepine, polysorbate 20, sodium chloride, animal experiment, animal model, animal tissue, article, Bagg albino mouse, brachydactyly, cesarean section, control group, controlled study, crown rump length, embryo, embryo development, exophthalmos, experimental study, eye development, eye malformation, female, fetus, fetus malformation, gestational age, mouse, nonhuman, organogenesis, pregnancy, retina fold, staining, teratogenesis, vertebra malformation, Abnormalities, Drug-Induced, Abnormalities, Multiple, Analgesics, Non-Narcotic, Animals, Anticonvulsants, Carbamazepine, Crown-Rump Length, Eating, Eye, Eye Abnormalities, Female, Fetal Weight, Gestational Age, Injections, Intraperitoneal, Mice, Mice, Inbred BALB C, Musculoskeletal Abnormalities, Organogenesis, Pregnancy, Risk Assessment, Teratogens, Mus
Subjects: مقالات نمایه شده محققین دانشگاه در سایت ,Web of Science ,Scopus
Divisions: معاونت تحقیقات و فناوری
Depositing User: GOUMS
Date Deposited: 18 Apr 2015 03:42
Last Modified: 10 Jun 2017 06:02
URI: http://eprints.goums.ac.ir/id/eprint/2222

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