Vitamins ameliorate secondary mitochondrial failure in neonatal rat brain

Recirculation after transient intrauterine ischemia has previously been found to be accompanied by secondary mitochondrial dysfunction in the immature rat brain. This study was performed to assess the efficacy of combined treatment with ascorbic acid and alpha-tocopherol in improving secondary brain damage. On the 17th day of gestation, transient intrauterine ischemia was induced by 30 minutes of uterine artery occlusion. Either vehicle, ascorbic acid, alpha-tocopherol, or combination of ascorbic acid and alpha-tocopherol was randomly administered to pregnant rats before and after occlusion. The pups were delivered by cesarean section at 21 days of gestation, and cerebral neocortical tissue was sampled. The mitochondrial respiration was measured polarographically in homogenates. In the ischemia uterine horn, mitochondrial activity of the vehicle treatment decreased significantly to 56% of nonischemic controls. Treatment with ascorbic acid or alpha-tocopherol alone demonstrated a moderate improvement of the secondary mitochondrial dysfunction to 64% and 62% of nonischemic controls, respectively. The combined treatment caused a normalization of mitochondrial activity to 91% of nonischemic controls. These results indicate that combined treatment with ascorbic acid and alpha-tocopherol has a more protective effect against secondary mitochondrial dysfunction after transient intrauterine ischemia compared with the administration of ascorbic acid or alpha-tocopherol alone.