Cutaneous and ocular toxicology · 2010
Teratogenic effects of carbamazepine on embryonic eye development in pregnant mice.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Afshar Mohammad, Moallem Seyed Adel, Houshang Mohammadpour Amir, Shiravi Abdolhossein, Majid Jalalian Seyed, Jafar Golalipour Mohammad
Аннотация
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 15 mg/kg (group I) or 30 mg/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.
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 15 mg/kg (group I) or 30 mg/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.
Предметные рубрики MeSH
Abnormalities, Drug-InducedAbnormalities, MultipleAnalgesics, Non-NarcoticAnimalsAnticonvulsantsCarbamazepineCrown-Rump LengthEatingEyeEye AbnormalitiesFemaleFetal WeightGestational AgeInjections, IntraperitonealMiceMice, Inbred BALB CMusculoskeletal AbnormalitiesOrganogenesisPregnancyRisk AssessmentTeratogens