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.
McIntosh
L J
LJ
Department of Biological Sciences, Stanford University, Stanford, CA 94305, USA. mcpenny@leland.stanford.edu
Cortopassi
K M
KM
Sapolsky
R M
RM
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D002374:Catalase / Q000378:metabolism*; D002531:Cerebellum / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D005979:Glutathione Peroxidase / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D051381:Rats; D013482:Superoxide Dismutase / Q000378:metabolism*
D000975:Antioxidants; D005938:Glucocorticoids; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D007608:Kainic Acid