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Visit our Expo - Redox and Inflammation signaling 2012

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Session XVII : Cell <strong>signaling</strong> in health <strong>and</strong> disease Poster XVII, 17<br />

Combined supplementation of folic acid <strong>and</strong> vitamin E diminishes diabetes-induced<br />

dysmorphogenesis in rat embryos<br />

Mattias Gäreskog, Ulf J Eriksson <strong>and</strong> Parri Wentzel<br />

Department of Medical Cell Biology, Uppsala University, Sweden<br />

Husargatan 3, Box 571, 751 23 Uppsala<br />

Mattias.Gareskog@medcellbiol.uu.se<br />

Diabetic embryopathy <strong>and</strong> growth disturbances are 3-5 fold more common in infants of<br />

diabetic mothers than in offspring of non-diabetic pregnancy. The mechanisms causing these<br />

disturbances are likely to be multifactorial.<br />

It has been suggested that oxidative stress <strong>and</strong> apoptosis plays an important roles during<br />

organogenesis. This notion may also be involved in the induction of embryonic<br />

dysmorphogenesis in diabetic pregnancy. We aimed to investigate the effect of administration<br />

of folic acid alone or combined with vitamin E on embryonic malformations <strong>and</strong> different<br />

markers of apoptosis, such as NFkB activity, Bcl-2, Bax protein levels <strong>and</strong> p-53 protein <strong>and</strong><br />

mRNA expression.<br />

Diabetes was induced by a single injection of streptozotocin. Pregnant, non-diabetic <strong>and</strong><br />

diabetic, rats were treated with daily injections of folic acid or treated with both folic acid <strong>and</strong><br />

5% vitamin E in the diet. Untreated rats from both groups served as controls. Embryos were<br />

collected on gestational day 10 or 11 <strong>and</strong> were evaluated with regard to malformations <strong>and</strong><br />

growth retardation. Some embryos were used for NFkB assay, western blot <strong>and</strong> cDNA<br />

synthesis.<br />

We found increased malformations <strong>and</strong> growth retardation in a diabetic milieu compared to<br />

normal environment. Supplementation of folic acid alone <strong>and</strong> combined with vitamin E<br />

normalized these parameters<br />

In addition, we found decreased NFkB activity <strong>and</strong> Bcl-2 protein, increased expression of Bax<br />

<strong>and</strong> p53 protein <strong>and</strong> mRNA in embryos of diabetic rats compared to normal rats.<br />

Administration of folic acid to the diabetic rats increased NFkB activity <strong>and</strong> Bcl-2 protein.<br />

Combined administration of folic acid <strong>and</strong> vitamin E normalized Bcl-2 expression in the<br />

diabetic environment.<br />

Combined folic acid <strong>and</strong> vitamin E supplementation to pregnant diabetic rats diminished<br />

diabetes-induced dysmorphogenesis <strong>and</strong> had several beneficial effects on embryonic<br />

apoptotic rate.<br />

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