Alpha-lipoic acid reduces congenital malformations in the offspring of diabetic mice.
BACKGROUND
The mechanism of diabetes-induced congenital malformation remains to be elucidated. It has been reported that alpha-lipoic acid (LA) prevents neural tube defects (NTDs) in offsprings of rats with streptozotocin-induced diabetes. Here, we evaluate the protective effect of LA against diabetic embryopathy, including NTDs, cardiovascular malformations (CVMs), and skeletal malformations, in mice.


METHODS
Female mice were rendered hyperglycemic using streptozotocin and then mated with normal male mouse. Pregnant diabetic or non-diabetic mice were treated daily with either LA (100 mg/kg body weight) or saline between gestational days 0 and 18. On day 18, fetuses were examined for congenital malformations.


RESULTS
Plasma glucose levels on day 18 were not affected by LA treatment. No congenital malformations were observed either in the saline-treated or LA-treated non-diabetic group. In the saline-treated diabetic group, 39% of fetuses had external malformations and 30% had NTDs. In the LA-treated diabetic group, the corresponding proportions were 11 and 8%, respectively. LA treatment also decreased the incidence of CVMs from 30-3% and of skeletal malformations from 29-6%.


CONCLUSIONS
We conclude that LA can reduce NTDs, CVMs and skeletal malformations in the offspring of diabetic mice at term delivery.
Sugimura
Y
Y
Department of Genetics, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Japan.
Murase
T
T
Kobayashi
K
K
Oyama
K
K
Hayasaka
S
S
Kanou
Y
Y
Oiso
Y
Y
Murata
Y
Y
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D018376:Cardiovascular Abnormalities / Q000517:prevention & control; D000013:Congenital Abnormalities / Q000517:prevention & control*; D003921:Diabetes Mellitus, Experimental / Q000097:blood; D005260:Female; D005327:Fetal Resorption; D005978:Glutathione / Q000378:metabolism; D008098:Litter Size / Q000187:drug effects; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D009436:Neural Tube Defects / Q000517:prevention & control*; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000097:blood; D008063:Thioctic Acid / Q000494:pharmacology*
D001786:Blood Glucose; D008063:Thioctic Acid; D005978:Glutathione