Combined supplementation of folic acid and vitamin E diminishes diabetes-induced embryotoxicity in rats

✍ Scribed by Mattias Gäreskog; Ulf J. Eriksson; Parri Wentzel

• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 251 KB
• Volume: 76
• Category: Article
• ISSN: 1542-0752
• DOI: 10.1002/bdra.20278

✦ Synopsis

Abstract

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.