Combined Supplementation of Folic Acid and Vitamin E Diminishes Diabetes-Induced Embryotoxicity in Rats
2006 (English)In: Birth defects research. Clinical and molecular teratology, ISSN 1542-0752, E-ISSN 1542-0760, Vol. 76, no 6, 483-490 p.Article in journal (Refereed) Published
BACKGROUND: Oxidative stress and enhanced apoptosis may be involved in the induction of embryonic dysmorphogenesis in diabetic pregnancy. Administration of folic acid or vitamin E diminishes embryonic dysmorphogenesis. We aimed to evaluate the effect of combined treatment with folic acid and vitamin E on the disturbed development in embryos of diabetic rats. METHODS: Pregnant nondiabetic and diabetic rats were treated with daily injections of 15 mg/kg folic acid or with 5% vitamin E in the diet. A third group received combined treatment. Day 10 and day 11 embryos were evaluated for development and apoptotic profile. RESULTS: We found increased malformations, resorptions, and profound growth retardation in embryos of diabetic rats compared to control embryos. Vitamin E or folic acid alone, or the 2 compounds combined, normalized embryonic demise. Maternal diabetes caused decreased nuclear factor-kappa B (NF-kappa B) activity and B-cell lymphoma 2 (Bcl-2) protein level, and increased Bcl-2-associated x proteins (Bax) in embryos. Supplementation of vitamin E alone normalized the Bax protein level in a diabetic environment. Administration of folic acid to diabetic rats increased NF-kappa B activity and Bcl-2 protein level. Combined treatment normalized Bcl-2 and Bax protein level in a diabetic environment. CONCLUSIONS: Combined supplementation of folic acid and vitamin E to pregnant diabetic rats diminished diabetes-induced malformations and resorptions, concomitant with normalization of apoptotic protein levels. No treatment completely abolished the embryonic demise; therefore, other mechanisms than oxidative stress and apoptosis are likely to be involved in diabetic embryopathy.
Place, publisher, year, edition, pages
2006. Vol. 76, no 6, 483-490 p.
embryopathy, rat, diabetes in pregnancy, folic acid, vitamin E, apoptosis
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-95026DOI: 10.1002/bdra.20278ISI: 000240271300007PubMedID: 16933212OAI: oai:DiVA.org:uu-95026DiVA: diva2:169079