title: Oxidative modification of the intestinal mucus layer is a critical but unrecognized component of trauma hemorrhagic shock-induced gut barrier failure.
abstract: Recent studies demonstrate that mechanisms underlying gut barrier failure include systemic processes and less studied luminal processes. We thus tested the hypothesis that mucus layer oxidation is a component of trauma/hemorrhagic shock-induced gut injury and dysfunction. Male Sprague-Dawley rats underwent trauma/hemorrhagic shock. Controls underwent trauma only. Mucus from the terminal 30 cm of the ileum was collected, processed, and analyzed for reactive nitrogen intermediates (RNI)-mediated damage, reactive oxygen species (ROS)-induced damage, and total antioxidant capacity. The distal ileum was stained to quantify the mucus layer; gut permeability was assessed physiologically. A time course study was conducted to determine the temporal sequence of mucus layer damage. The role of free radical-mediated damage to the gut barrier was investigated by the effect of the free radical scavenger dimethyl sulfoxide on trauma/hemorrhagic shock-induced changes on the mucus and on gut permeability. Trauma/hemorrhagic shock increased intestinal permeability, which was associated with evidence of loss of the unstirred mucus layer. These changes correlated with increased ROS- and RNI-mediated mucus damage and loss of mucus total antioxidant capacity. Based on the time course study, ROS-mediated mucus damage and loss of total antioxidant capacity were present immediately following shock, whereas RNI-mediated damage was delayed for 3 h. Dimethyl sulfoxide ameliorated gut barrier loss, ROS-mediated changes to the mucus layer, and loss of total antioxidant capacity. There was no change in RNI-induced changes to the mucus layer. These results support the hypothesis that trauma/hemorrhagic shock leads to mucus damage and gut dysfunction through the generation of free radical species.
authors.affiliation: Department of Surgery, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103, USA.
authors.forename: Jordan E
authors.initials: JE
authors.lastname: Fishman
authors.forename: Gal
authors.initials: G
authors.lastname: Levy
authors.forename: Vamsi
authors.initials: V
authors.lastname: Alli
authors.forename: Sharvil
authors.initials: S
authors.lastname: Sheth
authors.forename: Qu
authors.initials: Q
authors.lastname: Lu
authors.forename: Edwin A
authors.initials: EA
authors.lastname: Deitch
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000502:physiology; D007422:Intestines / Q000293:injuries* / Q000503:physiopathology; D008297:Male; D016877:Oxidants / Q000378:metabolism; D010084:Oxidation-Reduction; D010539:Permeability; D050050:Protein Carbonylation / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology; D012771:Shock, Hemorrhagic / Q000378:metabolism* / Q000503:physiopathology; D014443:Tyrosine / Q000378:metabolism
chemical_list: D000975:Antioxidants; D016166:Free Radical Scavengers; D016877:Oxidants; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D014443:Tyrosine; D004121:Dimethyl Sulfoxide