title: Effects of aspirin on gastroduodenal permeability in alcoholics and controls.
abstract: Alcohol and nonsteroidal anti-inflammatory drugs are noxious agents that can disrupt the integrity of the gastroduodenal mucosal and damage the epithelial barrier and lead to increased gastroduodenal permeability. Moreover, it is not uncommon that patients are exposed to these two barrier stressors at the same time. It is thus important to know how simultaneous exposure affects the gastroduodenal barrier, and acquiring that knowledge was the goal of this study. We used a method that has been widely used for the assessment of injury to the gastroduodenal barrier induced by these noxious agents-measurement of gastroduodenal permeability as indicated by urinary excretion of ingested sucrose. We used gas chromatography to measure the amount of sucrose excreted in the urine over the 5-12h after ingestion of a bolus of sucrose. The 148 participants in the study included 92 alcoholics and 56 healthy controls. All study subjects had a baseline permeability test. To determine whether addition of a second noxious agent, in addition to chronic alcohol, further decreases gastroduodenal barrier integrity, a subset of 118 study subjects participated in another permeability test in which they were exposed to aspirin. For this test, participants ingested 1,300 mg aspirin twice, 12 and 1h before the final permeability test. The baseline permeability test showed that alcoholics have significantly higher gastroduodenal permeability than controls. Aspirin caused a significant within-group absolute increase in gastroduodenal permeability in both alcoholics and controls (+7.72%, P=.003 and +2.25%, P=.011, respectively), but the magnitude of these increases was not significantly different from each other. Baseline permeability did vary by gender, self-reported illegal drug use, and employment type. The extent of the permeability increase after aspirin ingestion varied with illegal drug use and recruitment site (a surrogate marker of socioeconomic status). Our data show that alcoholics have greater gastroduodenal permeability than healthy controls. This difference was independent of the duration of any preceding period of sobriety, gender, smoking history, or illicit drug abuse. The injurious effects of alcohol on the gastroduodenal epithelial barrier are long lasting, persisting even after 7 days of sobriety. Although, acute aspirin and chronic alcohol each increase intestinal permeability in alcoholics, their effects appear to be additive rather than synergistic.
authors.affiliation: Department of Medicine, Rush University, Chicago, IL, USA.
authors.forename: Ashkan
authors.initials: A
authors.lastname: Farhadi
authors.forename: Ali
authors.initials: A
authors.lastname: Keshavarzian
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Kwasny
authors.forename: Maliha
authors.initials: M
authors.lastname: Shaikh
authors.forename: Louis
authors.initials: L
authors.lastname: Fogg
authors.forename: Cynthia
authors.initials: C
authors.lastname: Lau
authors.forename: Jeremy Z
authors.initials: JZ
authors.lastname: Fields
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Forsyth
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000503:physiopathology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000494:pharmacology; D001241:Aspirin / Q000009:adverse effects / Q000494:pharmacology*; D004064:Digestive System / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D010539:Permeability / Q000187:drug effects; D013395:Sucrose / Q000652:urine
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D013395:Sucrose; D001241:Aspirin