Sato M, Shirota M, Nagao T
Laboratory of Reproductive and Developmental Toxicology, Hatano Research Institute, Food and Drug Safety Center, Kanagawa, Japan.
Teratology. 1995 Sep;52(3):143-8. doi: 10.1002/tera.1420520306.
The effect of the administration of pantothenic acid (PTA) on valproic acid (VPA)-induced teratogenesis was examined in ICR mice. VPA (300, 400, and 500 mg/kg, s.c.) or PTA (3 x 10, 3 x 100, and 3 x 300 mg/kg, i.p.) was injected on day 8.5 of gestation (plug day = day 0.5). Exencephaly was induced dose dependently by single injections of VPA. Three administrations of PTA alone at any dose levels showed neither embryocidal nor teratogenic effects. In combined treatment experiments, PTA (3 x 300 mg/kg) was injected 1 hr before, immediately before, and 1 hr after VPA administration. PTA significantly reduced VPA-induced exencephaly, while none of the other external malformations such as open eyelid or skeletal malformations such as fused, absent, or bifurcated ribs and fused thoracic vertebrae and fused sternebrae were reduced. The results suggest that PTA reduces the incidence of neural tube defect induced by VPA in mice.
在ICR小鼠中研究了泛酸(PTA)给药对丙戊酸(VPA)诱导的致畸作用的影响。在妊娠第8.5天(见栓日=第0.5天)皮下注射VPA(300、400和500mg/kg)或腹腔注射PTA(3×10、3×100和3×300mg/kg)。单次注射VPA可剂量依赖性地诱发无脑畸形。在任何剂量水平下单独给予三次PTA均未显示出胚胎毒性或致畸作用。在联合治疗实验中,在VPA给药前1小时、给药前即刻和给药后1小时注射PTA(3×300mg/kg)。PTA显著降低了VPA诱导的无脑畸形,而其他外部畸形如眼睑开放或骨骼畸形如肋骨融合、缺失或分叉以及胸椎融合和胸骨融合均未减少。结果表明,PTA可降低小鼠中由VPA诱导的神经管缺陷的发生率。