Mechanism of dimethylsulfoxide protection against the teratogenicity of secalonic acid D in mice.
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.
ElDeib
M M
MM
Department of Veterinary Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia 65211.
Reddy
C S
CS
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002972:Cleft Palate / Q000139:chemically induced; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D005260:Female; D005327:Fetal Resorption; D005333:Fetus / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009183:Mycotoxins / Q000633:toxicity*; D011247:Pregnancy; D012016:Reference Values; D013723:Teratogens / Q000633:toxicity*; D014966:Xanthenes / Q000493:pharmacokinetics / Q000633:toxicity*; D044004:Xanthones
D009183:Mycotoxins; D013723:Teratogens; D014966:Xanthenes; D044004:Xanthones; C009218:secalonic acid; D004121:Dimethyl Sulfoxide