title: Ischemic preconditioning increases antioxidants in the brain and peripheral organs after cerebral ischemia.
abstract: OBJECTIVE
  Low molecular weight antioxidants (LMWA), which reflect tissue reducing power, are among the endogenous mechanisms for neutralizing reactive oxygen species (ROS). Ischemic preconditioning (IPC) was associated with decreased oxidative stress. We examined the effect of focal ischemia on LMWA and on prostaglandin E(2) (PGE(2), a product of arachidonic acid oxidation) in the brain, heart, liver, and lungs of rats subjected to 90 min of ischemia and in IPC rats subjected to similar insult.
  
  
  METHODS
  Transient right middle cerebral artery occlusion (MCAO) was performed for 90 min and at 0, 5, 30, 60, or 240 min of reperfusion, LMWA and PGE(2) were evaluated by cyclic voltametry (CV) and radioimmunoassay, respectively. IPC was induced by 2 min of MCAO, 24 h prior to the major ischemic episode.
  
  
  RESULTS
  LMWA decreased at 5 min of reperfusion in the brain, heart, liver, and lung and rose 4 h later only in the brain. PGE(2) levels increased three to fivefold in all tissues examined. Surprisingly, in IPC rats a dramatic increase of LMWA occurred at 5 min of reperfusion in the brain and in the peripheral organs. Uric acid, but not ascorbic, is the major LMWA increased.
  
  
  CONCLUSIONS
  We propose that after ischemia, ROS rapidly consume the antioxidants reserves in the brain and also in peripheral organs, suggesting that the whole body is under oxidative stress. Moreover, part of the neuroprotection afforded by IPC is mediated by the brain's ability to mobilize antioxidants, especially uric acid, that attenuate the massive ROS-mediated oxidative stress.
authors.affiliation: Department of Anesthesiology, Rabin Medical Center, Beilinson Campus, Israel.
authors.forename: Lucio
authors.initials: L
authors.lastname: Glantz
authors.forename: Aharon
authors.initials: A
authors.lastname: Avramovich
authors.forename: Victoria
authors.initials: V
authors.lastname: Trembovler
authors.forename: Vladimir
authors.initials: V
authors.lastname: Gurvitz
authors.forename: Ron
authors.initials: R
authors.lastname: Kohen
authors.forename: Leonid A
authors.initials: LA
authors.lastname: Eidelman
authors.forename: Esther
authors.initials: E
authors.lastname: Shohami
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D016718:Arachidonic Acid / Q000378:metabolism; D001205:Ascorbic Acid / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000503:physiopathology; D002545:Brain Ischemia / Q000378:metabolism* / Q000503:physiopathology; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D005609:Free Radicals / Q000378:metabolism*; D019194:Ischemic Preconditioning / Q000379:methods*; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology; D015854:Up-Regulation / Q000502:physiology; D014527:Uric Acid / Q000378:metabolism
chemical_list: D000975:Antioxidants; D005609:Free Radicals; D014527:Uric Acid; D016718:Arachidonic Acid; D015232:Dinoprostone; D001205:Ascorbic Acid