ElDeib M M, Reddy C S
Department of Veterinary Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia 65211.
Teratology. 1988 Nov;38(5):419-25. doi: 10.1002/tera.1420380504.
Dimethylsulfoxide (DMSO) is known to antagonize the teratogenic effects of secalonic acid D (SAD) in mice. To establish the optimum protective dose of DMSO, pregnant CD-1 mice were treated, i.p., with 30 mg/kg of SAD in 5% (w/v) NaHCO3, containing 0, 10, 20, or 30% (v/v) DMSO on day 11 of gestation. Data indicate that at 10% and 20% levels, DMSO affords an apparent dose-related protection against SAD-induced cleft palate, whereas 30% DMSO enhanced fetal resorption with no reduction in the incidence of cleft palate. Ultraviolet spectra and TLC mobility indicated that DMSO at 20% did not directly interact with SAD. Distribution and elimination of 14C-SAD was studied in fetal and maternal tissues from pregnant mice at 24 and 48 hr after exposure to 30 mg/kg of 14C-SAD, i.p., in NaHCO3 (control) or in 20% DMSO. Compared with those not receiving DMSO, maternal exposure to DMSO: 1) significantly reduced (42-75%) radioactivity in fetal heads and bodies, placenta, and maternal tissues other than liver; 2) significantly increased (up to 222%) the radioactivity in maternal liver; and 3) significantly reduced (44-58%) fecal and urinary elimination of SAD-derived radioactivity. These results suggest that the antiteratogenic effect of DMSO against SAD may be at least partly mediated by increased SAD (or its metabolites) retention by maternal liver leading to reduced SAD uptake by the fetus.
已知二甲基亚砜（DMSO）可拮抗小鼠中secalonic acid D（SAD）的致畸作用。为确定DMSO的最佳保护剂量，在妊娠第11天，给怀孕的CD-1小鼠腹腔注射含0、10、20或30%（v/v）DMSO的5%（w/v）NaHCO₃中的30 mg/kg SAD。数据表明，在10%和20%的水平下，DMSO对SAD诱导的腭裂具有明显的剂量相关保护作用，而30%的DMSO会增加胎儿吸收，且腭裂发生率没有降低。紫外光谱和薄层色谱迁移率表明，20%的DMSO不会与SAD直接相互作用。在怀孕小鼠腹腔注射30 mg/kg的¹⁴C-SAD（在NaHCO₃中（对照）或在20% DMSO中）后24和48小时，研究了¹⁴C-SAD在胎儿和母体组织中的分布和消除情况。与未接受DMSO的小鼠相比，母体接触DMSO：1）显著降低（42 - 75%）胎儿头部和身体、胎盘以及肝脏以外的母体组织中的放射性；2）显著增加（高达222%）母体肝脏中的放射性；3）显著减少（44 - 58%）SAD衍生放射性的粪便和尿液消除。这些结果表明，DMSO对SAD的抗致畸作用可能至少部分是由母体肝脏对SAD（或其代谢物）保留增加导致胎儿对SAD摄取减少介导的。
