关键词: Carbamazepine Craniofacial Embryo-fetal Malformation Skeletal Teratogenicity

Mesh : Animals Carbamazepine / toxicity Female Pregnancy Rats, Wistar Anticonvulsants / toxicity Administration, Oral Fetal Development / drug effects Abnormalities, Drug-Induced Maternal-Fetal Exchange Male Embryonic Development / drug effects Rats

来  源:   DOI:10.1016/j.reprotox.2024.108665

Abstract:
Carbamazepine is an anticonvulsant medication commonly used to treat epilepsy and other neurological disorders. The purpose of this study was to assess the impact of carbamazepine on prenatal development, including maternal-fetal, external, visceral, and skeletal toxicity. Additionally, the study aimed to investigate the effects of orally administered Carbamazepine at a lower dose range in Wistar rats. Pregnant female rats were randomly distributed into control (G1) group administered with distilled water orally (n=8), low dose (G2) group administered at 25 mg/kg, intermediate dose (G3) group at 50 mg/kg, and high dose (G4) group at 100 mg/kg through oral gavage from gestation day (GD) 5-19. Pregnant female rats were scheduled to necropsy on gestation day (GD) 20. During the evaluation, the uterus was observed for number of live or viable fetuses, dead fetuses, early resorptions, late resorptions, number of corpora lutea and the sex ratio (m/f) per litter. Further, fetuses were subjected to materno-fetal examination which included observation for placenta, amniotic fluid, and umbilical cord followed by external evaluation. Additionally, half of the fetuses were subjected to visceral, craniofacial evaluation and other half of the fetuses were subjected to skeletal evaluation by double staining method using Alcian Blue for cartilages and Alizarin Red S for bones. It was observed that there was a significant decrease in the rate of pregnancy in the intermediate dose (G3) group and in high dose (G4) group when compared with the control group. Moreover, treatment with the Carbamazepine caused significant increase in fetal malformations such as dilation of lateral and third ventricle in brain, in intermediate dose (G3) group and high dose (G4) group when compared with the control (G1) group, dilation of ureters in high dose (G4) group. Fetal skeletal malformations like bent and nodulated ribs were also observed in intermediate dose (G3) group. Existing research substantially supports the claim that carbamazepine can cause teratogenic effects and prenatal development toxicity even at a lower dose range.
摘要:
卡马西平是一种抗惊厥药物,通常用于治疗癫痫和其他神经系统疾病。这项研究的目的是评估卡马西平对产前发育的影响,包括母胎,外部,内脏,和骨骼毒性。此外,本研究旨在研究较低剂量范围口服卡马西平对Wistar大鼠的影响。雌性大鼠随机分为对照组(G1组),口服蒸馏水(n=8),低剂量(G2)组,25mg/kg,中剂量(G3)组,50mg/kg,和高剂量(G4)组,从妊娠日(GD)5-19天通过口服灌胃100mg/kg。计划在妊娠日(GD)20对妊娠雌性大鼠进行尸检。在评估过程中,观察子宫存活或存活胎儿的数量,死去的胎儿,早期吸收,晚期再吸收,黄体数量和每窝性别比(m/f)。Further,胎儿接受母胎检查,包括胎盘观察,羊水,和脐带,然后进行外部评估。此外,一半的胎儿受到内脏,颅面评估和胎儿的另一半通过双重染色法进行骨骼评估,使用AlcianBlue用于软骨,茜素红S用于骨骼。观察到,与对照组相比,中间剂量(G3)组和高剂量(G4)组的妊娠率显著降低。此外,卡马西平治疗导致胎儿畸形显着增加,如大脑中的侧脑室和第三脑室扩张,与对照组(G1)相比,中剂量(G3)组和高剂量(G4)组,大剂量(G4)组输尿管扩张。在中剂量(G3)组中还观察到胎儿骨骼畸形,例如弯曲和结节的肋骨。现有研究基本上支持卡马西平即使在较低剂量范围内也可引起致畸作用和产前发育毒性的说法。
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