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

Abstract

Objective: Increased oxidant stress has been suggested to play a role in the pathogenesis of disturbed embryogenesis in diabetic pregnancies. The present 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 made diabetic by a single intraperitoneal injection of streptozocin. Group 4 rats were injected with lipoic acid from day 1 to day 6, after vehicle treatment until day 17. At day 17 of gestation, rats were killed. The fetuses were released from the yolk sacs and surrounding decidua and were examined for size, resorption rate, and neural tube defects. Results: Pregnant diabetic rats treated with vehicle lost weight during pregnancy (−3.2 ± 1.9 g/d), as opposed to normal pregnancy-related weight gain (3.5 ± 0.5 g/d). Treatment with lipoic acid protected against diabetes-induced weight loss, without a measurable effect on fed-state glucose concentrations. Daily treatment with lipoic acid (pregnancy days 1 to 17) was efficient in reducing the resorption rate from 24.0% ± 9.5% in vehicle-treated 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 lipoic 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 (before diabetes induction), lipoic acid failed to exert its protective effects against neural tube defects, which emphasizes the importance of the presence of lipoic acid during the organogenesis period. The atherosis of placental 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 against diabetic embryopathy, fetal losses, and ultrastructural alteration of diabetic placentas. (Am J Obstet Gynecol 1999;180:188-93.)