Selective vulnerability to kainate-induced oxidative damage in different rat brain regions.
Some markers of oxidative injury were measured in different rat brain areas (hippocampus, cerebral cortex, striatum, hypothalamus, amygdala/piriform cortex and cerebellum) after the systemic administration of an excitotoxic dose of kainic acid (KA, 9 mg kg(-1) i.p.) at two different sampling times (24 and 48 h). Kainic acid was able to lower markedly (P < 0.05) the glutathione (GSH) levels in hippocampus, cerebellum and amygdala/piriform cortex (maximal reduction at 24 h). In a similar way, lipid peroxidation, as assessed by malonaldehyde and 4-hydroxyalkenal levels, significantly increased (P < 0.05) in hippocampus, cerebellum and amygdala/piriform cortex mainly at 24 h after KA. In addition, hippocampal superoxide dismutase (SOD) activity decreased significantly (P < 0.05) with respect to basal levels by 24 h after KA application. On the other hand, brain areas such as hypothalamus, striatum and cerebral cortex seem to be less susceptible to KA excitotoxicity. According to these findings, the pattern of oxidative injury induced by systemically administered KA seems to be highly region-specific. Further, our results have shown that a lower antioxidant status (GSH and SOD) seems not to play an important role in the selective vulnerability of certain brain regions because it correlates poorly with increases in markers of oxidative damage.
Candelario-Jalil
E
E
Department of Pharmacology, University of Havana (CIEB-IFAL), Apartado Postal 6079, Havana 10600, Cuba. ecjalil@cieb.sld.cu
Al-Dalain
S M
SM
Castillo
R
R
Martínez
G
G
Fernández
O S
OS
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007608:Kainic Acid / Q000008:administration & dosage / Q000633:toxicity*; D015227:Lipid Peroxidation; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism
D018691:Excitatory Amino Acid Antagonists; D011506:Proteins; D013482:Superoxide Dismutase; D005978:Glutathione; D007608:Kainic Acid