Health & Environmental Research Online (HERO)


Print Feedback Export to File
8611491 
Journal Article 
Late preconditioning by ethanol is initiated via an oxidant-dependent signaling pathway 
Yamaguchi, T; Dayton, CB; Ross, CR; Yoshikawa, T; Gute, DC; Korthuis, RJ 
2003 
Yes 
Free Radical Biology and Medicine
ISSN: 0891-5849
EISSN: 1873-4596 
ELSEVIER SCIENCE INC 
NEW YORK 
34 
3 
365-376 
English 
12543252 
WOS:000180501700008 
Ingestion of alcoholic beverages at low to moderate levels 24 h prior to ischemia and reperfusion (I/R) prevents postischemic leukocyte/endothelial cell adhesive interactions, a phenomenon referred to as late ethanol preconditioning (EtOH-PC). The aim of this study was to determine whether oxidants act as initiators of late EtOH-PC. Ethanol was instilled into the stomachs of C57BL/6 mice as a bolus by gavage at a dose that produced a peak plasma concentration of 45 mg/dl 30 min after administration and returned to control levels 60 min after ingestion. Twenty four hours later, the superior mesenteric artery was occluded for 45 min followed by 70 min of reperfusion. The numbers of rolling and firmly adherent leukocytes were quantified in postcapillary venules of the small intestine in sham animals (no EtOH-PC, no I/R), in mice subjected to I/R alone or EtOH-PC + I/R, and in animals treated with Mn-TBAP (a cell-permeant superoxide dismutase mimetic), oxypurinol (a XO inhibitor), the NAD(P)H oxidase inhibitors PR-39 or apocynin, or oxypurinol plus PR39 during the period of EtOH-PC on Day 1 followed by I/R on Day 2. In separate groups of mice, oxypurinol or apocynin were also administered 1 h after ethanol ingestion on Day 1, with induction of I/R 24 h later. I/R induced marked increases in leukocyte rolling and adherence, effects that were completely prevented by EtOH-PC. Coincident treatment with Mn-TBAP, oxypurinol, PR-39, apocynin, or oxypurinol plus PR-39 with ethanol attenuated these anti-inflammatory actions of EtOH-PC. However, administration of oxypurinol or apocynin I h after ethanol ingestion failed to prevent these protective effects of EtOH-PC. Our results indicate that reactive oxygen species formed during the period of ethanol exposure on Day 1 trigger the development of an anti-inflammatory phenotype that renders the small bowel resistant to the proadhesive effects of I/R 24 h later. (C) 2003 Elsevier Science Inc. 
late-phase ethanol preconditioning; ischemia; reperfusion; reactive; oxygen species; NAD(P)H oxidase; xanthine oxidase; leukocyte rolling; leukocyte adhesion; postcapillary venules; small intestine; C57/B16; free radicals; ischemia-reperfusion injury; acid porphyrin mntbap; oxidative stress; xanthine-oxidase; nitric-oxide; antimicrobial peptide; gene-expression; rabbit hearts; superoxide; Biochemistry & Molecular Biology; Endocrinology & Metabolism