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Phospholipid Degradation and Cellular Edema Induced by Free Radicals in Brain Cortical Slices
Authors:Pak Hoo Chan  Mary Yurko  Robert A. Fishman
Affiliation:Brain Edema Clinical Research Center, Department of Neurology, School of Medicine, University of California, San Francisco, California, U.S.A.
Abstract:Abstract: Cellular edema and increased lactate production were induced in rat brain cortical slices by xanthine oxidase and xanthine, in the presence of ferric ions. Lipid peroxidation, as measured by thiobarbituric acid-reactive malon-dialdehyde, was increased 174%. Among the various subcellular fractions of brain cortex, xanthine oxidase-stimulated lipid peroxidation was highest in myelin, mitochondria, and synaptosomes, followed by microsomes and nuclei. Antioxidants, catalase, chlorpromazine, and butylated hydroxytoluene inhibited lipid peroxidation in both homogenates and synaptosomes, indicating H2O2 and radicals were involved. Further, several free fatty acids, especially oleic acid (18:1), arachidonic acid (20:4), and docosahexaenoic acid (22:6) were released from the phospholipid pool concomitant with the degradation of membrane phospholipids in xanthine oxidase-treated synaptosomes. These data suggest that Upases are activated by free radicals and lipid peroxides in the pathogenesis of cellular swelling.
Keywords:Brain edema    Phospholipid degradation    Free radicals    Arachidonic acid    Polyunsaturated fatty acids
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