Afshar Mohammad, Hassanzadeh-Taheri Mohammad M, Moallem Seyed-Adel, Tamizi Azadeh, Golalipour Mohammad J
Department of Anatomy, Birjand University of Medical Sciences, Birjand, Iran.
Neurosciences (Riyadh). 2009 Jul;14(3):239-44.
To evaluate the effects of gabapentin (GBP) administration on mice fetuses.
This study was carried out in Birjand University of Medical Sciences during 2008. Thirty Balb/c pregnant mice were divided randomly into 3 groups: 2 experimental groups that received 25 mg/kg (I) and 50 mg/kg (II) of GBP intraperitoneally for the first 15 days of pregnancy, and a control group that received normal saline. External observations of day 18 fetuses and skeleton double staining were performed.
Both experimental groups showed similar disorders that can be categorized as the following: 1) decrease of fetal body weight and increase of fetal resorption, 2) macroscopic malformations, and 3) skeletal malformations. Fetal body weights were significantly lower, and fetus resorptions were significantly higher in both treated groups compared to the control group. Macroscopic malformations included exencephaly, limbs defects, brachygnathia, vertebral column deformity, and fetuses with severe retarded growth. Skeletal malformations included delayed ossification, scoliosis, calvaria deformity, and mandibular hypoplasia.
This study revealed that GBP can induce previously unreported severe malformations if it is used continuously during the implantation, neurulation, and organogenesis stages of pregnancy. Therefore, it is suggested that great caution should be exercised in using GBP during the early stages of pregnancy until further studies are performed to better understand these effects.
评估加巴喷丁(GBP)给药对小鼠胎儿的影响。
本研究于2008年在比尔詹德医科大学开展。30只Balb/c怀孕小鼠被随机分为3组:2个实验组,在怀孕的前15天腹腔注射25mg/kg(I组)和50mg/kg(II组)的GBP,以及1个接受生理盐水的对照组。对第18天的胎儿进行外观观察并进行骨骼双重染色。
两个实验组均出现了类似的异常情况,可归类如下:1)胎儿体重下降和胎儿吸收增加,2)肉眼可见的畸形,3)骨骼畸形。与对照组相比,两个治疗组的胎儿体重均显著降低,胎儿吸收显著增加。肉眼可见的畸形包括无脑儿、肢体缺陷、小颌畸形、脊柱畸形以及生长严重迟缓的胎儿。骨骼畸形包括骨化延迟(骨化迟缓)、脊柱侧弯、颅骨畸形和下颌发育不全。
本研究表明,如果在怀孕的植入、神经胚形成和器官发生阶段持续使用GBP,可诱发此前未报道的严重畸形。因此,建议在怀孕早期使用GBP时应格外谨慎,直至进行进一步研究以更好地了解这些影响。