Article Text

  1. W. S. Jaber1,
  2. P. C. Joshi1,
  3. D. M. Guidot1
  1. 1Atlanta VAMC and Emory University, Atlanta, GA


Alcohol abuse independently increases the risk of developing the acute respiratory distress syndrome (ARDS) two- to fourfold in critically ill patients with sepsis, trauma, or massive gastric aspiration. We have shown in experimental animal models that chronic alcohol ingestion causes oxidative stress within the alveolar space, impairs alveolar epithelial barrier integrity, and increases sepsis-mediated acute lung injury. However, the precise mechanisms by which alcohol abuse renders the lung susceptible to injury are still under investigation. Alcoholics are known to be deficient in the essential micronutrient zinc (Zn), which is critical for diverse cellular functions within the respiratory tract, including stabilization of membranes and tissue repair. Therefore, we hypothesized that Zn deficiency in the alveolar space may contribute significantly to the cellular dysfunction and increased epithelial permeability in the “alcoholic lung” and that these defects could be corrected by Zn supplementation. Male Sprague-Dawley rats were fed the Lieber-DeCarli liquid diet ± alcohol for 6 weeks. Zn acetate (0.2%) was added to the alcohol diets of some rats. Alveolar epithelial cells were isolated from each rat and grown to monolayer confluence (8 days), at which time the permeability was determined by measuring the flux of radiolabeled sucrose across each monolayer. In some experiments, Zn acetate (1-20 μM) was added to the alveolar epithelial cell monolayers in vitro to determine whether Zn had any direct effects on the alcoholic airway epithelium. Chronic alcohol ingestion significantly increased the alveolar epithelial permeability compared with control-fed rats. Zinc supplements, either in vivo or in vitro, significantly decreased the alcohol-induced abnormal permeability in the alveolar epithelium, and in the in vitro experiments, this protective effect of Zn was concentration dependent. Interestingly, Zn treatment, either in vivo or in vitro, appeared to increase the expression of the tight junction proteins occludin and ZO-1 as assessed by fluorescence microscopy. These results suggest that Zn deficiency, in part through changes in tight junction assembly and/or function, may be one of the mechanisms by which alcohol abuse impairs alveolar epithelial barrier integrity and increases the susceptibility to acute lung injury. We speculate that Zn supplementation could improve alveolar epithelial barrier function and decrease the incidence and/or severity of acute lung injury in this highly vulnerable patient population.

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