Combined supplementation of folic acid and vitamin E diminishes diabetes-induced embryotoxicity in rats.
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-kappaB (NF-kappaB) 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-kappaB 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.
Gäreskog
Mattias
M
Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden. Mattias.Gareskog@medcellbiol.uu.se
Eriksson
Ulf J
UJ
Wentzel
Parri
P
D000818:Animals; D000013:Congenital Abnormalities / Q000517:prevention & control*; D019587:Dietary Supplements; D005260:Female; D005327:Fetal Resorption / Q000517:prevention & control; D005492:Folic Acid / Q000627:therapeutic use*; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000178:diet therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014810:Vitamin E / Q000627:therapeutic use*
D014810:Vitamin E; D005492:Folic Acid