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  • 1
    ISSN: 1432-0428
    Keywords: Keywords Diabetic pregnancy ; embryo development ; congenital malformation ; glucose ; β-hydroxybutyrate ; branched chain amino acids ; embryo culture ; superoxide dismutase ; N-acetylcysteine.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 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 β-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 β-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 antiteratogenic 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. [Diabetologia (1997) 40: 7–14]
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Keywords Diabetic pregnancy ; streptozotocin ; rat ; embryo ; fetus ; congenital malformation ; vitamin C ; antioxidant therapy ; TBARS ; oxidative stress.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary An excess of reactive oxygen species (ROS) has been associated with the increased rate of congenital malformations in experimental diabetic pregnancy. Previous in vitro and in vivo studies show that antioxidants can protect the embryonic development in a diabetic environment. In the present investigation we examined the antiteratogenic capacity of vitamin C, an antioxidative agent not previously evaluated as a dietary supplement in diabetic pregnancy. Normal and streptozotocin diabetic rats were either fed a standard diet or a diet enriched with 0.9, 1.8 or 4 % sodium ascorbate throughout pregnancy. On gestational day 20, the litters of normal and diabetic rats without vitamin C supplement contained 9 and 12 % early resorptions, 2 and 17 % late resorptions and 1 and 27 % malformations, respectively. Vitamin C treatment reduced the rates of late resorptions and malformations in the diabetic groups in proportion to the dose administered. Thus, in the diabetic group with 4 % ascorbate treatment we found unchanged numbers of early resorptions, but only 7 % late resorptions (p 〈 0.05 vs untreated diabetic pregnancy) and 8 % malformations (p 〈 0.05 vs untreated diabetic pregnancy). Maternal diabetes did not alter tissue levels of ascorbic acid in the fetuses at term, whereas vitamin C treatment caused accumulation of ascorbic acid in the placenta, maternal and fetal liver. Vitamin C supplementation yielded increased α-tocopherol concentration in the placenta and caused a reduction of the high concentrations of thiobarbituric acid reactive substances (TBARS) in serum of pregnant diabetic rats. Vitamin C treatment reduces the rates of congenital malformations and late resorptions, thereby supporting that ROS are involved in the embryonic dysmorphogenesis of diabetic pregnancy. [Diabetologia (1997) 40: 1416–1424]
    Type of Medium: Electronic Resource
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