Antioxidative treatment diminishes ethanol-induced congenital malformations in the rat.
BACKGROUND
Intrauterine exposure to ethanol causes embryonic and fetal growth retardation and maldevelopment. Oxidative stress in mother and offspring has been suggested to be part of the teratogenic mechanism, and supplementation of antioxidative agents to the pregnant women may therefore be of value in future prophylactic treatment regimen. There is a need for in vivo experimental work in this field, and in the present study, our aim was to investigate whether chronic ethanol consumption induced congenital malformations in rats and, if so, whether dietary supplementation of vitamin E (alpha-tocopherol) diminished such maldevelopment.


METHODS
Female Sprague-Dawley rats were given drinking water containing 20% ethanol and half of these received food containing 5% vitamin E. Non-ethanol-exposed female rats, with or without vitamin E treatment, served as controls. The pregnancy was interrupted on gestational day 20 when the offspring was evaluated morphologically and fetal hepatic 8-iso-PGF(2alpha) levels were measured to assess the degree of fetal oxidative stress.


RESULTS
Exposure to 20% ethanol increased maternal blood ethanol to 1.5 promille and increased resorption and malformation rates in the offspring. Maternal vitamin E treatment did not affect blood ethanol levels, but normalized fetal development. The fetal hepatic levels of 8-iso-PGF(2alpha) were increased in the ethanol-exposed group and normalized by vitamin E treatment of the mother.


CONCLUSIONS
Ethanol exposure disturbs embryogenesis partly by enhanced oxidative stress, and the adverse effects can be ameliorated by antioxidative treatment.
Wentzel
Parri
P
Department of Medical Cell Biology, Uppsala Universitet, Biomedical Center, Uppsala, Sweden. Parri.Wentzel@medcellbiol.uu.se
Rydberg
Ulf
U
Eriksson
Ulf J
UJ
D000014:Abnormalities, Drug-Induced / Q000517:prevention & control*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002492:Central Nervous System Depressants / Q000009:adverse effects* / Q000097:blood / Q000494:pharmacology; D015237:Dinoprost / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism; D047108:Embryonic Development / Q000187:drug effects; D000431:Ethanol / Q000009:adverse effects* / Q000097:blood / Q000494:pharmacology; D005260:Female; D005317:Fetal Growth Retardation / Q000209:etiology / Q000517:prevention & control; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000209:etiology / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D024502:alpha-Tocopherol / Q000494:pharmacology*
D000975:Antioxidants; D002492:Central Nervous System Depressants; C075750:8-epi-prostaglandin F2alpha; D000431:Ethanol; D015237:Dinoprost; D024502:alpha-Tocopherol