Increased cerebral ischemic damage during chronic alcohol consumption: role of NAD(P)H oxidase

Abstract

We hypothesized that NAD(P)H oxidase may contribute to increased cerebral ischemic damage during chronic alcohol consumption. Sprague‐Dawley rats were randomly divided into four groups: nonalcohol‐fed, alcohol‐fed, nonalcohol‐fed plus apocynin‐treated, and alcohol‐fed plus apocynin‐treated. Alcohol (8 g/kg/day) was mixed into a liquid diet and given to rats for 8 weeks. Apocynin (7.5 mg/kg/day) was orally administrated for 4 weeks prior to the experiment. Rats were subjected to 2 hours of right middle cerebral artery occlusion (MCAO). Infarct volume and neurological score were assessed 24 hours after reperfusion. Superoxide production from ischemic border area was measured by lucigenin‐enhanced chemiluminescence. In addition, expression of NAD(P)H oxidase membrane subunit gp91phox in ischemic border area was analyzed by Western blot. Compared with nonalcohol‐fed rats, alcohol‐fed rats had a larger infarct volume, worse neurological score and higher superoxide production. Apocynin did not alter infarct size, neurological deficit or superoxide production in nonalcohol‐fed rats, but significantly reduced infarct size, improved neurological outcome and attenuated superoxide production in alcohol‐fed rats. Chronic alcohol consumption significantly increased gp91 phox expression compared with nonalcohol‐fed rats, and cerebral ischemia also significantly enhanced gp91 phox expression compared with nonischemic side. Apocynin treatment did not alter gp91 phox expression in either nonalcohol‐fed rats or alcohol‐fed rats. Our findings suggest that NAD(P)H oxidase may play an important role in increased cerebral ischemic damage during chronic alcohol consumption.