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Atorvastatin protects against cerebral infarction via inhibition of NADPH oxidase-derived superoxide in ischemic stroke.
- Source :
-
American journal of physiology. Heart and circulatory physiology [Am J Physiol Heart Circ Physiol] 2006 Nov; Vol. 291 (5), pp. H2210-5. Date of Electronic Publication: 2006 Jun 09. - Publication Year :
- 2006
-
Abstract
- Statins have recently been shown to exert neuronal protection in ischemic stroke. Reactive oxygen species, specifically superoxide formed during the early phase of reperfusion, augment neuronal injury. NADPH oxidase is a key enzyme for superoxide production. The present study tested the hypothesis that atorvastatin protects against cerebral infarction via inhibition of NADPH oxidase-derived superoxide in transient focal ischemia. Transient focal ischemia was created in halothane-anesthetized adult male Sprague-Dawley rats (250-300 g) by middle cerebral artery occlusion (MCAO). Atorvastatin (Lipitor, 10 mg/kg sc) was administered three times before MCAO. Infarct volume was measured by triphenyltetrazolium chloride staining. NADPH oxidase enzymatic activity and superoxide levels were quantified in the ischemic core and penumbral regions by lucigenin (5 microM)-enhanced chemiluminescence. Expression of NADPH oxidase membrane subunit gp91(phox) and membrane-translocated subunit p47(phox) and small GTPase Rac-1 was analyzed by Western blot. NADPH oxidase activity and superoxide levels increased after reperfusion and peaked within 2 h of reperfusion in the penumbra, but not in the ischemic core, in MCAO rats. Atorvastatin pretreatment prevented these increases, blunted expression of membrane subunit gp91(phox), and prevented translocation of cytoplasmic subunit p47(phox) to the membrane in the penumbra 2 h after reperfusion. Consequently, cerebral infarct volume was significantly reduced in atorvastatin-treated compared with nontreated MCAO rats 24 h after reperfusion. These results indicate that atorvastatin protects against cerebral infarction via inhibition of NADPH oxidase-derived superoxide in transient focal ischemia.
- Subjects :
- Animals
Atorvastatin
Cerebral Infarction etiology
Cerebral Infarction metabolism
Disease Models, Animal
Male
NADPH Oxidases analysis
NADPH Oxidases genetics
Nitric Oxide Synthase Type II metabolism
Rats
Rats, Sprague-Dawley
Superoxides analysis
Time Factors
Cerebral Infarction prevention & control
Heptanoic Acids pharmacology
NADPH Oxidases metabolism
Neuroprotective Agents pharmacology
Pyrroles pharmacology
Superoxides antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 0363-6135
- Volume :
- 291
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Heart and circulatory physiology
- Publication Type :
- Academic Journal
- Accession number :
- 16766636
- Full Text :
- https://doi.org/10.1152/ajpheart.01270.2005