Ethanol-induced teratogenesis: free radical damage as a possible mechanism.
To investigate the possibility of a free radical mechanism for ethanol-induced teratogenesis, gestational day 8 mouse embryos were exposed for 6 hr in whole embryo culture to a teratogenic dosage of ethanol alone (500 mg%) or in conjunction with an antioxidant, superoxide dismutase (SOD; 300 U/ml). For subsequent analysis, some embryos were examined at the end of this 6-hr period, while others were removed to control medium and cultured for an additional time period. Ethanol exposure resulted in increased superoxide anion generation and increased lipid peroxidation (as noted 6 hr after initial ethanol exposure) and in excessive cell death (as noted 12 hr after initial exposure) in the embryos. Following a total of 36 hr in culture, a high incidence of malformation, including failure of the anterior neural tube to close in 63% of the ethanol-exposed embryos, was noted. The ethanol-induced superoxide anion generation, lipid peroxidation, excessive cell death, and dysmorphogenesis were diminished in embryos co-treated with SOD, suggesting that the teratogenicity of ethanol is mediated, at least in part, by free radical damage.
Kotch
L E
LE
Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Chen
S Y
SY
Sulik
K K
KK
D000014:Abnormalities, Drug-Induced / Q000378:metabolism / Q000517:prevention & control; D000818:Animals; D004347:Drug Interactions; D004622:Embryo, Mammalian / Q000187:drug effects; D005314:Embryonic and Fetal Development / Q000187:drug effects; D000431:Ethanol / Q000633:toxicity*; D005147:Facial Bones / Q000002:abnormalities*; D005260:Female; D016166:Free Radical Scavengers / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009436:Neural Tube Defects / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control; D009924:Organ Culture Techniques; D011247:Pregnancy; D012886:Skull / Q000002:abnormalities*; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism
D016166:Free Radical Scavengers; D005609:Free Radicals; D013481:Superoxides; D000431:Ethanol; D013482:Superoxide Dismutase