Protection against oxidative damage to CNS by alpha-phenyl-tert-butyl nitrone (PBN) and other spin-trapping agents: A novel series of nonlipid free radical scavengers

Journal Article · Tue Jan 01 00:00:00 EST 1991 · Journal of Molecular Neuroscience; (United States)

DOI:https://doi.org/10.1007/BF02896848· OSTI ID:5017322

Carney, J M; Floyd, R A ^[1]

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1. Department of Pharmacology, Chandler Medical Center, University of Kentucky, Lexington (United States)

Brain is extremely susceptible to oxidative damage. Utilizing a series of novel approaches, the authors have demonstrated that oxidative damage occurs during an ischemia/reperfusion insult (IRI) to brain. Thus, they have demonstrated that an IRI to Mongolian gerbil brain results in: (1) an enhanced rate of salicylate hydroxylation, implicating an increased flux of hydroxyl free radicals; (2) an enhanced flux of free radicals as determined by spin-trapping; (3) an enhanced level of endogenous protein oxidation; (4) a decrease in glutamine synthetase (GS) activity, an enzyme very sensitive to oxidative damage; and (5) demonstration of protection from an IRI by administering the spin-trapping agent alpha-phenyl-tert-butyl nitrone (PBN). The novel observation that PBN offers protection from the lethality brought on by a brain IRI appears to be clearly linked to the ability of the administered spin-trap to inhibit oxidative damage as evidenced by the decreased amount of brain protein oxidation and the prevention of an IRI-mediated loss of GS activity in treated animals. Aged gerbils are more sensitive to the lethal action of a brain IRI than younger animals, but they are protected by PBN administration as are the younger animals. Older gerbils have a significantly higher level of oxidized protein in the brain. Older gerbils have decreased activities of GS and neutral protease, the enzyme that removes oxidized protein, than younger animals. Chronic twice daily administration of PBN (32 mg/kg) for 14 days to older animals significantly lowered brain oxidized protein levels and raised GS and neutral protease activity to those observed in younger animals. Cessation of PBN administration resulted in a time-dependent restoration of protein oxidation levels and enzyme activities back to those observed prior to spin-trap administration.

• OSTI ID: 5017322
• Journal Information: Journal of Molecular Neuroscience; (United States), Vol. 3:1; ISSN 0895-8696
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
BRAIN
SENSITIVITY
NITROGEN OXIDES
BIOLOGICAL EFFECTS
RADICALS
BIOSYNTHESIS
AGE DEPENDENCE
ELECTRON SPIN RESONANCE
ENZYME ACTIVITY
GERBILS
ISCHEMIA
OXYGEN
PEPTIDE HYDROLASES
REDOX REACTIONS
TIME DEPENDENCE
ANEMIAS
ANIMALS
BODY
CARDIOVASCULAR DISEASES
CENTRAL NERVOUS SYSTEM
CHALCOGENIDES
CHEMICAL REACTIONS
DISEASES
ELEMENTS
ENZYMES
HEMIC DISEASES
HYDROLASES
MAGNETIC RESONANCE
MAMMALS
NERVOUS SYSTEM
NITROGEN COMPOUNDS
NONMETALS
ORGANS
OXIDES
OXYGEN COMPOUNDS
RESONANCE
RODENTS
SYMPTOMS
SYNTHESIS
VASCULAR DISEASES
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology