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PBN Reversal of Brain Aging

proctorp at delphi.com proctorp at delphi.com
Thu Feb 16 21:13:22 EST 1995


Carney JM  Floyd RA
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.

In: J Mol Neurosci (1991) 3(1):47-57

Brain is extremely susceptible to oxidative damage. Utilizing
  a series of novel approaches, we have demonstrated that
  oxidative damage occurs during an ischemia/reperfusion
  insult (IRI) to brain. Thus, we 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. Older gerbils exhibit significantly higher
  errors in a radial arm maze than younger
  animals, but older gerbils that had received chronic daily
  treatments  of PBN (32 mg/kg) for 14 days committed
  significantly less errors than untreated controls. The
  errors committed in PBN-treated animals
  was decreased down to the level of those observed in
  younger animals.

  Clearly the spin-trapping agent, PBN, appears to have
  promise in: (1)elucidation of the role of oxidative damage
  in normal brain function during aging, (2) understanding
  the development of pathological  conditions, and (3)
  development of treatment regimens for prevention
  of damage that occurs during the development of
  pathological conditions and in aging.

Institutional address:
     Department of Pharmacology
     Chandler Medical Center
     University of Kentucky
     Lexington 40536.

PS:  PBN is patented in Europe as a hair-growth
stimulator.  Does make it a bit relevant.

Peter H. Proctor, PhD, MD
(713) 960-1616

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