Mechanism of dimethylsulfoxide protection against the teratogenicity of secalonic acid D in mice.
Mechanism of dimethylsulfoxide protection against the teratogenicity of secalonic acid D in mice.
复制标题
二甲亚砜对小鼠癸二酸D致畸作用的保护机制。
DOI：
10.1002/tera.1420380504
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
Reddy,CS
中科院分区：
文献类型：
--
作者：
ElDeib,MM;Reddy,CS
二甲亚砜（DMSO）可以拮抗小鼠中的secalonic acid D（SAD）的致畸作用。为了确定DMSO的最佳保护剂量，将妊娠CD-1小鼠腹膜内处理，在妊娠第11天给予含0、10、20或30%（v/v）DMSO的5%（w/v）NaHCO 3中的30 mg/kg SAD。数据表明，在10%和20%水平下，DMSO对SAD诱导的腭裂提供了明显的剂量相关保护，而30% DMSO增强了胎仔吸收，但未降低腭裂的发生率。紫外光谱和TLC迁移率表明，20%的DMSO不直接与SAD相互作用。在暴露于30 mg/kg 14 C-SAD（i. p.）后24和48 h，研究了妊娠小鼠胎仔和母体组织中14 C-SAD的分布和消除，在NaHCO 3（对照）中或在20%DMSO中。与未接受DMSO的动物相比，母体暴露于DMSO：（1）胎仔头部和身体、胎盘和母体组织（肝脏除外）中的放射性显著降低（42-75%）;（2）母体肝脏中的放射性显著增加（高达222%）;（3）SAD衍生放射性的粪便和尿液消除显著降低（44-58%）。这些结果表明，DMSO对SAD的抗致畸作用可能至少部分是通过母体肝脏增加SAD（或其代谢产物）保留，导致胎儿SAD摄取减少来介导的。
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 of14C‐SAD was studied in fetal and maternal tissues from pregnant mice at 24 and 48 hr after exposure to 30 mg/kg of14C‐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.