Firat Deniz, Kuntsal Leyla, Sirin Yigit
Department of Oral Surgery, School of Dentisry, Istanbul University, Turkey.
Tohoku J Exp Med. 2005 Jan;205(1):27-36. doi: 10.1620/tjem.205.27.
Craniofacial malformations are among the most common congenital deformities. Meckel's cartilage plays a major role in the development of the mandible and is highly susceptible to maternal teratogenic drug use. We therefore investigated possible protective effects of prenatal administration of folic acid on a retinoic-acid induced maxillofacial defect model. Sprague-Dawley pregnant female rats (n=36) were used in this study. Retinoic acid was administered orally at the dose of 40, 60, or 80 mg/kg respectively on gestational day 8. Folic acid of 4.0 mg/kg was injected intraperitoneally on 7th, 8th and 9th days of pregnancy. Animals were sacrificed on the day 17th. Administration of retinoic acid at all doses resulted in statistically significant decreases in mean fetal weight and mean fetal height and the increase in mortality rate, and caused severe ultrastructural damages in Meckel's cartilage. Folic acid administration prevented the decrease in mean fetal weight and height of the embryos treated with retinoic acid of 40 mg/kg. In addition, there was a marked decrease in the number of degenerated chondrocytes and an improvement in the structure of granular endoplasmic reticulum along with intact nuclei. We conclude that folic acid has protective effects on retinoic acid-induced intracellular damages in Meckel's cartilage.
颅面畸形是最常见的先天性畸形之一。梅克尔软骨在下颌骨发育中起主要作用，且极易受到母体致畸药物的影响。因此，我们研究了产前给予叶酸对维甲酸诱导的颌面缺损模型的可能保护作用。本研究使用了36只Sprague-Dawley怀孕雌性大鼠。在妊娠第8天分别以40、60或80mg/kg的剂量口服维甲酸。在妊娠第7、8和9天腹腔注射4.0mg/kg的叶酸。在第17天处死动物。所有剂量的维甲酸给药均导致平均胎儿体重和平均胎儿身高在统计学上显著降低，死亡率增加，并导致梅克尔软骨严重的超微结构损伤。叶酸给药可防止用40mg/kg维甲酸处理的胚胎的平均胎儿体重和身高下降。此外，退化软骨细胞数量明显减少，颗粒内质网结构改善，细胞核完整。我们得出结论，叶酸对维甲酸诱导的梅克尔软骨细胞内损伤具有保护作用。
