Lipoic acid prevention of neural tube defects in offspring of rats with streptozocin-induced diabetes

OBJECTIVE: Increased oxidant stress has been suggested to play a role in th e pathogenesis of disturbed embryogenesis in diabetic pregnancies. The pres ent study was conducted to determine whether administration of lipoic acid, a naturally occurring antioxidant, would reduce the incidence of diabetic embryopathy in the streptozocin-induced diabetic rat model. STUDY DESIGN: After conception, rats were randomly distributed to 5 groups. From day 1, rats were daily injected intraperitoneally with either lipoic acid, 30 mg/kg, or vehicle. At day 6, rats from groups 3, 4, and 5 were mad e diabetic by a single intraperitoneal injection of streptozocin. Group 4 r ats were injected with lipoic acid from day 1 to day 6, after vehicle treat ment until day 17. At day 17 of gestation, rats were kilted. The fetuses we re released from the yolk sacs and surrounding decidua and were examined fo r size, resorption rate, and neural tube defects. RESULTS: Pregnant diabetic rats treated with vehicle lost weight during pre gnancy (-3.2 +/- 1.9 g/d), as opposed to normal pregnancy-related weight ga in (3.5 +/- 0.5 g/d). Treatment with lipoic acid protected against diabetes -induced weight loss, without a measurable effect on fed-state glucose conc entrations. Daily treatment with lipoic acid (pregnancy days 1 to 17) was e fficient in reducing the resorption rate from 24.0% +/- 9.5% in vehicle-tre ated diabetic rats to 10.2% +/- 4.8% in lipoic acid-treated diabetic rats ( P < .05). The rate of neural tube defects in diabetic rats treated with lip oic acid throughout the pregnancy was reduced from 26.0% +/- 7.0% to 10.2% +/- 3.2% (P < .05). In rats treated only during pregnancy days 1 to 5 (befo re diabetes induction), lipoic acid failed to exert its protective effects against neural tube defects, which emphasizes the importance of the presenc e of lipoic acid during the organogenesis period. The atherosis of placenta l vasculature demonstrated in the vehicle-treated diabetic rats was absent from placentas obtained from lipoic acid-treated diabetic animals. CONCLUSIONS: Our data demonstrate a protective effect of lipoic acid agains t diabetic embryopathy, fetal losses, and ultrastructural alteration of dia betic placentas.