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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. 291(5)
- 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 μM)-enhanced chemiluminescence. Expression of NADPH oxidase membrane subunit gp91phox and membrane-translocated subunit p47phox 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 gp91phox, and prevented translocation of cytoplasmic subunit p47phox 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 :
- Male
Time Factors
Physiology
Atorvastatin
Nitric Oxide Synthase Type II
Pharmacology
medicine.disease_cause
Rats, Sprague-Dawley
chemistry.chemical_compound
Superoxides
Physiology (medical)
Medicine
Animals
Pyrroles
cardiovascular diseases
chemistry.chemical_classification
Reactive oxygen species
NADPH oxidase
biology
business.industry
Superoxide
Cerebral infarction
NADPH Oxidases
Cerebral Infarction
medicine.disease
Rats
Disease Models, Animal
Neuroprotective Agents
chemistry
Biochemistry
Heptanoic Acids
Ischemic stroke
biology.protein
Cardiology and Cardiovascular Medicine
business
Early phase
Oxidative stress
medicine.drug
Subjects
Details
- ISSN :
- 03636135
- Volume :
- 291
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- American journal of physiology. Heart and circulatory physiology
- Accession number :
- edsair.doi.dedup.....04264c859ba38ac26f85fce520b7e05a