Teratogenic effect of diabetic serum is prevented by supplementation of superoxide dismutase and N-acetylcysteine in rat embryo culture.
Congenital malformations are more common in offspring of diabetic mothers than offspring of non-diabetic mothers. The precise cell biological mechanism leading to the increased incidence of congenital malformations in diabetic pregnancy is not known. In previous studies increased glucose and beta-hydroxybutyrate concentrations were found to cause embryonic dysmorphogenesis. We have previously shown that rat embryos, cultured in serum from insulin-treated diabetic rats, develop malformations, despite normalisation of glucose and beta-hydroxybutyrate concentration, thereby suggesting a multifactorial teratological nature of the diabetic environment. In the present study, therefore, we aimed to characterise the teratogenic activity of various components of diabetic serum and in addition to study the possible anti-teratogenic effects of supplementation of superoxide dismutase and N-acetylcysteine in rat embryo culture. We found that diabetic serum has a teratogenic effect on embryo development, a capacity residing in the alteration of several serum components in addition to glucose. Improving the embryonic capability to scavenge oxygen radicals, either by increasing superoxide dismutase activity or by supplying a rate-limiting precursor (N-acetylcysteine) for the enhanced synthesis of reduced glutathione, blocks the embryonic dysmorphogenesis.
Wentzel
P
P
Department of Medical Cell Biology, University of Uppsala, Sweden.
Thunberg
L
L
Eriksson
U J
UJ
D000111:Acetylcysteine / Q000494:pharmacology*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000097:blood*; D004622:Embryo, Mammalian / Q000187:drug effects / Q000378:metabolism; D005314:Embryonic and Fetal Development; D005260:Female; D016166:Free Radical Scavengers / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000196:embryology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000494:pharmacology*; D013723:Teratogens / Q000494:pharmacology*; D013997:Time Factors
D016166:Free Radical Scavengers; D013723:Teratogens; D013482:Superoxide Dismutase; D000111:Acetylcysteine