Presented at the 13th annual meeting of European Cell Death Organization, 1–4 October 2005, Budapest, Hungary.
Combined supplementation of folic acid and vitamin E diminishes diabetes-induced embryotoxicity in rats†
Article first published online: 24 AUG 2006
Copyright © 2006 Wiley-Liss, Inc.
Birth Defects Research Part A: Clinical and Molecular Teratology
Volume 76, Issue 6, pages 483–490, June 2006
How to Cite
Gäreskog, M., Eriksson, U. J. and Wentzel, P. (2006), Combined supplementation of folic acid and vitamin E diminishes diabetes-induced embryotoxicity in rats. Birth Defects Research Part A: Clinical and Molecular Teratology, 76: 483–490. doi: 10.1002/bdra.20278
- Issue published online: 24 AUG 2006
- Article first published online: 24 AUG 2006
- Manuscript Accepted: 1 MAY 2006
- Manuscript Revised: 28 APR 2006
- Manuscript Received: 24 NOV 2005
- Swedish Research Council. Grant Numbers: 12X-7475, 12X-109
- Ernfors Family Fund
- Swedish Diabetes Association
- Novo Nordisk Foundation
- diabetes in pregnancy;
- folic acid;
- vitamin E;
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–κB (NF-κB) 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-κB 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. Birth Defects Research (Part A) 76:483–490, 2006. © 2006 Wiley-Liss, Inc.