Teratogenic effects of carbamazepine on embryonic eye development in pregnant mice

Afshar, Mohammad; Moallem, Seyed Adel; Mohammadpour, Amir Hooshang; Shiravi, Abdolhossein; Jalalian, Seyed Majid; Golalipour, Mohammad Jafar

doi:10.3109/15569520903380353

Cited by 18 publications

(17 citation statements)

References 19 publications

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“…In this study, various doses of VA were administered, and it was concluded that the survival rate of the embryos decreased as the dose increased. Among older generation anti-epileptics, carbamazepine, and phenytoin, although at a relatively low rate, have been shown to cause neural defects [9,13]. The fact that administering these two medications at the same dosage resulted in different rates of neural tube defect suggests that the affected biochemical paths are different [8].…”

Section: Discussionmentioning

confidence: 99%

Comparison of the effects of levetiracetam and valproic acid on neural tube defect formation in the chick embryo: an experimental study

Asan¹

2019

Ann Clin Anal Med

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Aim: The aim of this study is to compare the dosage-related effects of levetiracetam and valproic acid on neural tube defect formation in chick embryos, when applied as monotherapy and in combination. Material and Method: A total of 360 fertilized pathogens-free white-Leghorn eggs were used in the study. The eggs were allowed to incubate for 72 hours. Total of six groups were formed where each medication was administered in low (250 mcg) and high (500 mcg) doses and in combination. Results obtained from the control and sham groups were compared. Results: The prevalence of NTD was found to be significantly lower in the group that received levetiracetam compared to the group that was treated with valproic acid. It was determined that NTD prevalence increased with a dosage increase in both groups. The prevalence of NTD was found to be significantly higher in groups where the two medications were administered in combination compared to the groups that received a single medication. Discussion: Both levetiracetam and valproic acid have the potential to create NTD. Valproic acid has a higher potential of creating NTD compared to levetiracetam. The likeliness of causing NTD significantly increases depending on dosage for both medications. Both medications have the potential to create NTD during pregnancy and must be used with caution.

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Section: Discussionmentioning

confidence: 99%

Comparison of the effects of levetiracetam and valproic acid on neural tube defect formation in the chick embryo: an experimental study

Asan¹

2019

Ann Clin Anal Med

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“…[21819] Afshar et al ., also showed that intraperitoneal administration of CBZ at clinical doses induced several open eye malformations in mice. [11]…”

Section: Discussionmentioning

confidence: 99%

“…showed that there was weight reduction of mice on the 1 st day of delivery regardless of the dose of CBZ. [11] Eye malformations like mild to severe exophthalmos and skeletal deformities such as vertebral and calvarial deformities, brachydactyly and short tail were detected in mice fetuses. In a published article, studying the teratogenic effects albino mice, a significant decrease of body weight, individual organ weight, upper and lower limb length of mice and congenital anomalies such as spina bifida, anencephaly, and oligodactyly were noted in offspring of mice treated with CBZ.…”

Section: Introductionmentioning

confidence: 99%

Teratogenic effects of carbamazepine in mice

Jose

Sreelatha

James

et al. 2017

Ann Indian Acad Neurol

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Objectives:The aim of this study was to determine the teratogenic effects of carbamazepine (CBZ) in BALB/c mice.Materials and Methods:Mature female and male BALB/c mice (25–30 g) were used for all experiments. After standardization of administration and dose of CBZ, animals in the CBZ-treated groups (CBZ 450 mg/kg and 600 mg/kg) were fed on medicinal diet. The dams in the control group were mated on the same day as that of the CBZ-treated dams. After cesarean section (CS), fetal viability status and weights were recorded. Gross histopathological examination of fetuses was conducted to identify alterations in morphology and external or internal organs due to in utero exposure of CBZ.Results:Out of the nine female animals (three treated on CBZ 450 mg/kg, three treated on CBZ 600 mg/kg and three controls), seven were pregnant, and two (one each from the two CBZ-treated groups) were nonpregnant. All fetuses of the control group (n = 31) and CBZ 450 mg/kg treated group (n = 24) were live, but eight out of the twenty fetuses (40%) of CBZ 600 mg/kg treated group were dead at CS. The birth weight of the fetuses antenatally exposed to CBZ was drastically reduced (0.71 ± 0.06) when compared to control fetuses (1.67 ± 0.12) (P < 0.0001). All the fetuses of the CBZ-treated groups showed stunted physical development.Conclusion:Although oral administration of CBZ to mice is a convenient model to study the effect of CBZ to pregnancy, higher oral dose was associated with increased fetal loss. Some of the fetuses exposed to CBZ demonstrated structural abnormalities and low body weight.

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“…In a landmark 1995 pharmacokinetics study, carbamazepine (CBZ) was shown not only to cross the intestinal barrier but also the blood brain barrier in rats [25]. More worrisome, studies have also identified teratogenic effects of carbamazepine including abnormal embryonic eye development upon administartion at clinical doses to pregnant mice [26]. These studies suggest that carbamazepine could be a potent teratogen during pregnancy.…”

Section: Discussionmentioning

confidence: 99%

Maternal exposure to carbamazepine at environmental concentrations can cross intestinal and placental barriers

Kaushik

Huber

Aho

et al. 2016

Biochemical and Biophysical Research Communications

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Psychoactive pharmaceuticals have been found as teratogens at clinical dosage during pregnancy. These pharmaceuticals have also been detected in minute (ppb) concentrations in drinking water in the US, and are environmental contaminants that may be complicit in triggering neurological disorders in genetically susceptible individuals. Previous studies have determined that psychoactive pharmaceuticals (fluoxetine, venlafaxine and carbamazepine) at environmentally relevant concentrations enriched sets of genes regulating development and function of the nervous system in fathead minnows. Altered gene sets were also associated with potential neurological disorders, including autism spectrum disorders (ASD). Subsequent in vitro studies indicated that psychoactive pharmaceuticals altered ASD-associated synaptic protein expression and gene expression in human neuronal cells. However, it is unknown if environmentally relevant concentrations of these pharmaceuticals are able to cross biological barriers from mother to fetus, thus potentially posing risks to nervous system development. The main objective of this study was to test whether psychoactive pharmaceuticals (fluoxetine, venlafaxine, and carbamazepine) administered through the drinking water at environmental concentrations to pregnant mice could reach the brain of the developing embryo by crossing intestinal and placental barriers. We addressed this question by adding 2H-isotope labeled pharmaceuticals to the drinking water of female mice for 20 days (10 pre-and 10 post-conception days), and quantifying 2H-isotope enrichment signals in the dam liver and brain of developing embryos using isotope ratio mass spectrometry. Significant levels of 2H enrichment was detected in the brain of embryos and livers of carbamazepine-treated mice but not in those of control dams, or for fluoxetine or venlafaxine application. These results provide the first evidence that carbamazepine in drinking water and at typical environmental concentrations is transmitted from mother to embryo. Our results, combined with previous evidence that carbamazepine may be associated with ASD in infants, warrant the closer examination of psychoactive pharmaceuticals in drinking water and their potential association with neurodevelopmental disorders.

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Teratogenic effects of carbamazepine on embryonic eye development in pregnant mice

Cited by 18 publications

References 19 publications

Comparison of the effects of levetiracetam and valproic acid on neural tube defect formation in the chick embryo: an experimental study

Comparison of the effects of levetiracetam and valproic acid on neural tube defect formation in the chick embryo: an experimental study

Teratogenic effects of carbamazepine in mice

Maternal exposure to carbamazepine at environmental concentrations can cross intestinal and placental barriers

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