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Maternal exposure to busulfan reduces the cell number in the somatosensory cortex associated with delayed somatic and reflex maturation in neonatal rats
Journal of Chemical Neuroanatomy ( IF 2.7 ) Pub Date : 2020-01-01 , DOI: 10.1016/j.jchemneu.2019.101710
Henrique J C B Gouveia 1 , Raul Manhães-de-Castro 2 , Bárbara J R Costa-de-Santana 3 , Carolina R Mendonça 1 , Glayciele Albuquerque 4 , Diego Bulcão Visco 1 , Diego Cabral Lacerda 1 , Ana Elisa Toscano 5
Affiliation  

Busulfan is a bifunctional alkylating agent used for myeloablative conditioning and in the treatment of chronic myeloid leukemia due to its ability to cause DNA damage. However, in rodent experiments, busulfan presented a potential teratogenic and cytotoxic effect. Studies have evaluated the effects of busulfan on fetuses after administration in pregnancy or directly on pups during the lactation period. There are no studies on the effects of busulfan administration during pregnancy on offspring development after birth. We investigated the effects of busulfan on somatic and reflex development and encephalic morphology in young rats after exposure in pregnancy. The pregnant rats were exposed to busulfan (10 mg/kg, intraperitoneal) during the early developmental stage (days 12-14 of the gestational period). After birth, we evaluated the somatic growth, maturation of physical features and reflex-ontogeny during the lactation period. We also assessed the effects of busulfan on encephalic weight and cortical morphometry at 28 days of postnatal life. As a result, busulfan-induced pathological changes included: microcephaly, evaluated by the reduction of cranial axes, delay in reflex maturation and physical features, as well as a decrease in the morphometric parameters of somatosensory and motor cortex. Thus, these results suggest that the administration of a DNA alkylating agent, such as busulfan, during the gestational period can cause damage to the central nervous system in the pups throughout their postnatal development.

中文翻译:

母体暴露于白消安可减少与新生大鼠躯体和反射成熟延迟相关的体感皮层中的细胞数量

白消安是一种双功能烷化剂,由于其能够引起 DNA 损伤,因此用于清髓性调理和治疗慢性粒细胞白血病。然而,在啮齿动物实验中,白消安表现出潜在的致畸和细胞毒性作用。研究评估了白消安在怀孕期间对胎儿或在哺乳期直接对幼崽施用后对胎儿的影响。目前尚无关于孕期服用白消安对后代出生后发育影响的研究。我们研究了白消安对孕期暴露后幼鼠的躯体和反射发育以及脑形态学的影响。妊娠大鼠在早期发育阶段(妊娠期第 12-14 天)暴露于白消安(10 毫克/千克,腹膜内)。出生后,我们评估了哺乳期的体细胞生长、身体特征的成熟和反射性个体发育。我们还评估了白消安对出生后 28 天脑重量和皮质形态测量的影响。因此,白消安引起的病理变化包括:小头畸形,通过颅轴的减少、反射成熟和身体特征的延迟以及躯体感觉和运动皮层的形态测量参数降低来评估。因此,这些结果表明,在妊娠期使用 DNA 烷化剂,如白消安,会在幼崽出生后的整个发育过程中对中枢神经系统造成损害。我们还评估了白消安对出生后 28 天脑重量和皮质形态测量的影响。因此,白消安引起的病理变化包括:小头畸形,通过颅轴的减少、反射成熟和身体特征的延迟以及躯体感觉和运动皮层的形态测量参数降低来评估。因此,这些结果表明,在妊娠期使用 DNA 烷化剂(如白消安)会在幼崽出生后的整个发育过程中对中枢神经系统造成损害。我们还评估了白消安对出生后 28 天脑重量和皮质形态测量的影响。因此,白消安引起的病理变化包括:小头畸形,通过颅轴的减少、反射成熟和身体特征的延迟以及躯体感觉和运动皮层的形态测量参数降低来评估。因此,这些结果表明,在妊娠期使用 DNA 烷化剂(如白消安)会在幼崽出生后的整个发育过程中对中枢神经系统造成损害。以及体感和运动皮层的形态测量参数降低。因此,这些结果表明,在妊娠期使用 DNA 烷化剂(如白消安)会在幼崽出生后的整个发育过程中对中枢神经系统造成损害。以及体感和运动皮层的形态测量参数降低。因此,这些结果表明,在妊娠期使用 DNA 烷化剂(如白消安)会在幼崽出生后的整个发育过程中对中枢神经系统造成损害。
更新日期:2020-01-01
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