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.

Figure 1. The effect of chronic alcohol consumption and acute aspirin intake on gastroduodenal permeability

Gastroduodenal permeability (urinary sucrose excretion) for all study subjects (n=49 healthy controls and n=69 alcoholics) at baseline and after aspirin challenge are presented. Urinary sucrose excretion was determined by GC analysis after an oral sugar bolus as described in Methods. Data are presented as standardized scores (see Methods) of medians of percent of oral sucrose dose excreted in the urine (5 or 12 hours). Note that: 1) Alcoholics have significantly higher sucrose excretion (leaky gastroduodenal barrier) than Controls (*, p=.004); and 2) Aspirin induces a significant increase in gastroduodenal permeability in both Controls (**, p=.011) and Alcoholics (***, p=.003).

Figure 2. Stability of gastroduodenal permeability in alcoholic and healthy control subjects

Figure 2 depicts gastroduodenal permeability (urinary sucrose) for those subjects for whom two baseline measurements were taken one week apart (Weeks 1 & 2) and after aspirin challenge (n=35 healthy controls and n=54 alcoholics). Gastroduodenal permeability was determined as described in Fig 1. Data are presented as means of percent of oral sucrose dose excreted in the urine (5 or 12 hours). Data shown are non-standardized as the second baseline test (Week 2) was only available for those with 12 hour collections. Note that: 1) There were no statistically significant within-group differences between baseline time points (Weeks 1 & 2). However, there is more baseline variability in the Alcoholic group, although no correlation was found between permeability and length of sobriety. 2) Alcoholics had greater gastroduodenal permeability to sucrose at both baseline tests compared to Controls. 3) Overall, aspirin increased gastroduodenal permeability to sucrose in both Controls and Alcoholics, especially in those who had lower baseline values.