Amelioration of brain damage after focal ischemia in the rat by a novel inhibitor of lipid peroxidation.
We studied the effects of 2-(allyl-1-piperazinyl)-4-n-amyloxyquinazoline fumarate (KB-5666) on brain edema and histological neuronal damage in rats with focal ischemia and on lipid peroxidation in brain homogenates and brain mitochondria in vitro. KB-5666 (3-100 microM) inhibited lipid peroxidation in brain homogenates and mitochondria, and also inhibited mitochondrial swelling. In a rat with middle cerebral artery occlusion, administration of KB-5666 (3 and 10 mg/kg) immediately after ischemia prevented the formation of brain edema in the cortex and ameliorated the histological neuronal damage in the same area, but failed to do so in the striatum. These results indicate that KB-5666 is a potential inhibitor of lipid peroxidation that could possibly prevent ischemic complications such as formation of brain edema and neuronal damage. Further, these results suggest that lipid peroxidation may play an important role in the pathogenesis of ischemic damage after focal ischemia.
Hara
H
H
Department of Neurology, Institute of Brain Diseases, Tohoku University School of Medicine, Sendai, Japan.
Kogure
K
K
Kato
H
H
Ozaki
A
A
Sukamoto
T
T
D000818:Animals; D001921:Brain / Q000473:pathology; D001929:Brain Edema / Q000188:drug therapy / Q000473:pathology; D001930:Brain Injuries / Q000188:drug therapy* / Q000209:etiology; D002545:Brain Ischemia / Q000150:complications*; D002536:Cerebral Arteries / Q000187:drug effects; D005990:Glycerol / Q000378:metabolism; D066298:In Vitro Techniques; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D008933:Mitochondrial Swelling / Q000187:drug effects; D011799:Quinazolines / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains
D011799:Quinazolines; C066472:KB 5666; D005990:Glycerol