Preconditioning by an in situ administration of hydrogen peroxide: involvement of reactive oxygen species and mitochondrial ATP-dependent potassium channel in a cerebral ischemia-reperfusion model.
Reactive oxygen species (ROS) and the mitochondrial ATP-dependent potassium channel (mitoK(+)(-)(ATP)) play a major role in myocardial preconditioning. The same pathways seem to be involved in cerebral preconditioning. The aim of this study was to evaluate ROS involvement during the initial phase of delayed preconditioning and its relationship with mitoK(+)(-ATP) opening in a rat model of cerebral ischemia-reperfusion. Ischemia was induced by a 1-h occlusion of middle cerebral artery followed by a 24-h reperfusion period. A delayed preconditioning was induced by a 3-min ischemia (IPC), an in situ infusion of hydrogen peroxide (H(2)O(2)), or an administration of mitoK(+)(-ATP) agonist diazoxide, 72 h before the ischemia-reperfusion (I/R). IPC was performed in the presence or not of N-acetyl-cysteine (NAC) or 5-hydroxydecanoate (5-HD). A neuroprotection was induced by IPC and administration of H(2)O(2) or diazoxide. The decrease in infarct size was respectively 24.5%, 45.7% and 24.6%. IPC was abolished by 5-HD and NAC, indicating that mitoK(+)(-ATP) and ROS are involved. The protection induced by H(2)O(2) was blocked by 5-HD and diazoxide triggering was abolished by NAC. This strong relationship between ROS and mitoK(+)(-ATP) needs to be clarified as ROS might be involved both upstream and downstream of mitoK(+)(-ATP) opening.
Simerabet
Malika
M
Department of Pharmacology, Faculty of Medicine, University of Lille2, France.
Robin
Emmanuel
E
Aristi
Ines
I
Adamczyk
Sebastien
S
Tavernier
Benoit
B
Vallet
Benoit
B
Bordet
Régis
R
Lebuffe
Gilles
G
D000818:Animals; D006861:Hydrogen Peroxide / Q000008:administration & dosage*; D020925:Hypoxia-Ischemia, Brain / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D007276:Injections, Intraventricular; D019194:Ischemic Preconditioning / Q000379:methods; D008297:Male; D016877:Oxidants / Q000008:administration & dosage*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015427:Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*
D016877:Oxidants; D015221:Potassium Channels; D017382:Reactive Oxygen Species; C117780:mitochondrial K(ATP) channel; D006861:Hydrogen Peroxide