Ischemic preconditioning increases antioxidants in the brain and peripheral organs after cerebral ischemia.
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.
Glantz
Lucio
L
Department of Anesthesiology, Rabin Medical Center, Beilinson Campus, Israel.
Avramovich
Aharon
A
Trembovler
Victoria
V
Gurvitz
Vladimir
V
Kohen
Ron
R
Eidelman
Leonid A
LA
Shohami
Esther
E
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
D000975:Antioxidants; D005609:Free Radicals; D014527:Uric Acid; D016718:Arachidonic Acid; D015232:Dinoprostone; D001205:Ascorbic Acid