Glucocorticoids may alter antioxidant enzyme capacity in the brain: kainic acid studies

Glucocorticoids (GCs) predispose hippocampal neurons to damage during metabolic stressors. One component of hippocampal GC-endangerment may be changes in neuronal defenses against oxidative challenge. Previous experiments showed a decrease in basal levels of copper/zinc superoxide dismutase (Cu/Zn SOD) and glutathione peroxidase (GSPx) in the brain of rats treated with GCs [L. McIntosh, K. Hong, R. Sapolsky, Glucocorticoids may alter antioxidant enzyme capacity in the brain: baseline studies, 1997.]. In this study we administered the excitotoxin kainic acid (KA) to generate reactive oxygen species (ROS) in the brain, and monitored the activity of four antioxidant enzymes over 24 h in GC-free and GC-supplemented rats. We tested the response pattern in three regions of the brain (hippocampus, cortex, cerebellum) and the liver as a peripheral control. In the hippocampus, KA induced Cu/Zn SOD and catalase, but GCs prevented the induction of catalase and maintained the lowered GSPx activity seen previously in the baseline studies. In the cortex, KA induced Cu/Zn SOD, Mn SOD and catalase activity, but there was no significant GC effect. There was no response to KA in the cerebellum, but GCs decreased GSPx activity. In the liver, KA produced a rise in Cu/Zn SOD and catalase activity, and GC-treated animals showed a slower return to baseline. These experiments indicate that the impairment of antioxidant enzyme defenses, particularly the hippocampal peroxidases, could be a component of GC-mediated neuroendangerment.