title: Apocynin protects against global cerebral ischemia-reperfusion-induced oxidative stress and injury in the gerbil hippocampus.
abstract: Increased production of reactive oxygen species (ROS) following cerebral ischemia-reperfusion (I/R) is an important underlying cause for neuronal injury leading to delayed neuronal death (DND). In this study, apocynin, a specific inhibitor for NADPH oxidase, was used to test whether suppression of ROS by the NADPH oxidase inhibitor can protect against ischemia-induced ROS generation and decrease DND. Global cerebral ischemia was induced in gerbils by a 5-min occlusion of bilateral common carotid arteries (CCA). Using measurement of 4-hydroxy-2-nonenal (HNE) as a marker for lipid peroxidation, apocynin (5 mg/kg body weight) injected i.p. 30 min prior to ischemia significantly attenuated the early increase in HNE in hippocampus measured at 3 h after I/R. Apocynin also protected against I/R-induced neuronal degeneration and DND, oxidative DNA damage, and glial cell activation. Taken together, the neuroprotective effects of apocynin against ROS production during early phase of I/R and subsequent I/R-induced neuronal damage provide strong evidence that inhibition of NADPH oxidase could be a promising therapeutic mechanism to protect against stroke damage in the brain.
authors.affiliation: Department of Biochemistry, M743 Medical Sciences Building, University of Missouri-Columbia, Columbia, MO 65212, USA.
authors.forename: Qun
authors.initials: Q
authors.lastname: Wang
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Tompkins
authors.forename: Agnes
authors.initials: A
authors.lastname: Simonyi
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Korthuis
authors.forename: Albert Y
authors.initials: AY
authors.lastname: Sun
authors.forename: Grace Y
authors.initials: GY
authors.lastname: Sun
mesh_terms: D000098:Acetophenones / Q000494:pharmacology*; D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002544:Cerebral Infarction / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D004249:DNA Damage / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005849:Gerbillinae; D005911:Gliosis / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009410:Nerve Degeneration / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000098:Acetophenones; D000447:Aldehydes; D000975:Antioxidants; D015415:Biomarkers; D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; C056165:acetovanillone; D019255:NADPH Oxidases; C027576:4-hydroxy-2-nonenal