Chronic ethanol ingestion increases susceptibility to acute lung injury: role of oxidative stress and tissue remodeling.
Clinical studies have demonstrated that chronic alcohol abuse is an independent outcome variable in acute lung injury. The Emory Center for the Study of Acute Lung Injury is determining the mechanisms by which ethanol increases susceptibility to acute lung injury. We developed a rat model of chronic ethanol ingestion and demonstrated that ethanol predisposes rats to edematous lung injury elicited by endotoxemia or sepsis. Chronic ethanol ingestion in rats led to decreased levels of glutathione, an important antioxidant in the lung, and this defect was associated with alterations in epithelial cell permeability, decreased alveolar liquid clearance, decreased cell viability, and decreased surfactant production. Chronic ethanol ingestion also led to the activation of lung tissue remodeling as demonstrated by the increased expression of profibrotic growth factors, matrix components, and metalloproteases. In cultured fibroblasts, the induction of the matrix glycoprotein fibronectin by ethanol was mediated via nicotinic acetylcholine receptor-dependent signal transduction. We speculate that these alterations render the host susceptible to acute lung injury by diminishing the protective mechanisms of the lung and promoting exaggerated inflammatory and tissue repair responses elicited against injurious agents.
Guidot
David M
DM
Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, Atlanta Veterans Affairs Medical Center, Emory University School of Medicine, Atlanta, GA, USA.
Roman
Jesse
J
D019973:Alcohol-Related Disorders / Q000150:complications*; D000818:Animals; D000431:Ethanol / Q000009:adverse effects*; D005353:Fibronectins / Q000502:physiology; D005978:Glutathione / Q000502:physiology; D006801:Humans; D008168:Lung / Q000503:physiopathology; D023421:Models, Animal; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D012128:Respiratory Distress Syndrome / Q000139:chemically induced* / Q000503:physiopathology
D005353:Fibronectins; D000431:Ethanol; D005978:Glutathione