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Ethanol preconditioning protects against ischemia/reperfusion‐induced brain damage: Role of NADPH oxidase‐derived ROS
Author(s) -
Wang Qun,
Sun A. Y.,
Simonyi A.,
Tompkins K. D.,
Guo J. J.,
Sun G. Y.,
Korthuis R. J.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1389-b
Subject(s) - apocynin , nadph oxidase , neuroprotection , oxidative stress , pharmacology , chemistry , reactive oxygen species , ischemia , reperfusion injury , biochemistry , medicine
Ethanol preconditioning (EtOH‐PC) refers to a phenomenon in which tissues are protected from the deleterious effects of ischemia/reperfusion (I/R) by prior ingestion of ethanol at low to moderate levels. We tested whether administration of ethanol by a dose protocol that produced a peak plasma concentration of 42–46 mg/dl in gerbils, 24 hrs prior to cerebral I/R would be neuroprotective. We also determined whether ROS‐derived from NADPH oxidase played a role as an initiator of these protective effects. Ethanol was gavaged 24 h prior to global I/R‐induced by occlusion of both CCA for 5 min, and apocynin, a inhibitor of NADPH oxidase, was administered (5 mg/kg body wt, i.p.) 10 min before ethanol administration. EtOH‐PC protected the brain against I/R‐induced delayed neuronal death, neuronal and dendritic degeneration, oxidative DNA damage, and glial cell activation, beneficial effects that were attenuated by apocynin treatment coincident with ethanol administration. Ethanol ingestion was associated with increased ROS production in plasma and hippocampus within the first 2 hrs after gavage, as demonstrated by increased levels of 4‐hydroxynonenal (HNE), an effect that was also inhibited by concomitant apocynin treatment. These results are consistent with the hypothesis that antecedent ethanol ingestion at socially‐relevant levels induces neuroprotective effects in I/R by a mechanism that is triggered by ROS formed by NADPH oxidase. Our results suggest the possibility that other pharmacological agents that induce a mild oxidative stress may have therapeutic value for suppressing stroke‐mediated damage in brain (supported by NIH AG18357, DK 43785 and AA14945).