We have recently demonstrated the evidence of oxidative stress in brain of immature rats during
seizures induced by
DL-homocysteic acid (DL-HCA). The aim of the present study was to investigate the
antioxidant defense mechanisms under these conditions.
Seizures were induced in immature 12-day-old rats by bilateral icv infusion of DL-HCA (600 nmol/side), and the activities of the main
antioxidant enzymes were examined in supernatants of the cerebral cortex during the acute phase of
seizures and at several periods of survival, up to 5 weeks, following these
seizures. In control animals individual
antioxidant enzymes revealed different changes during the studied postnatal period (PD 12 till PD 47). Total
superoxide dismutase (SOD), CuZn SOD (SOD1),
Mn SOD (SOD2) and
glutathione peroxidase (GPX) activities were increasing while,
catalase activity decreased and the activity of
glutathione reductase (GR) remained unchanged. In HCA-treated animals, the activity of total SOD, SOD1 and particularly SOD2 significantly increased at 20 h and 6 days of survival. Importantly, upregulation of SOD2 was also confirmed in mitochondria at the
protein level by immunoblotting. The activities of other
antioxidant enzymes including
catalase and GPX did not significantly differ upon HCA treatment from the appropriate controls at any of the studied time intervals. The pronounced and selective upregulation of SOD2 points to enhanced ROS levels in the mitochondrial matrix. This may be associated with inhibition of respiratory chain complex I that we have demonstrated in our previous studies. The present findings suggest that oxidative stress occurring in the brain of immature rats during and following the
seizures induced by DL-HCA is apparently due to both the increased
free radical production and the limited
antioxidant defense.