title: Inhibition of NADPH oxidase prevents acute lung injury in obese rats following severe trauma.
abstract: Lung capillary filtration coefficient (Kf) and impacts of oxidative stress have not been determined in the setting of severe trauma, especially in obese patients who exhibit increased lung injury. We hypothesized that severe trauma leads to a greater increase in lung Kf in obesity due to exacerbated production of and/or vulnerability to oxidative stress. Severe trauma was induced in lean and obese Zucker rats by muscle injury, fibula fracture, and bone component injection to both hindlimbs, with or without 24-h treatments of apocynin, a NADPH oxidase (NOX) inhibitor. Lung wet/dry weight ratios, lung vascular Kf, lung neutrophil counts, lung NOX and myeloperoxidase (MPO) activity, and plasma IL-6 levels were measured 24 h after trauma. In an additional study, lungs were isolated from nontrauma lean and obese rats to determine the acute effect of phenazime methosulfate, a superoxide donor, on pulmonary vascular Kf. After trauma, compared with lean rats, obese rats exhibited greater increases in lung capillary Kf, neutrophil accumulation, NOX and MPO activity, and plasma IL-6. The lung wet/dry weight ratio was increased in obese rats but not in lean rats. Apocynin treatment decreased lung Kf, neutrophil counts, NOX and MPO activities, wet/dry weight ratio, and plasma IL-6 in obese rats. Phenazime methosulfate treatment resulted in a greater increase in lung Kf in nontrauma obese rats compared with nontrauma lean rats. These results suggest that obese rats are susceptible to lung injury following severe trauma due to increased production of and responsiveness to pulmonary oxidative stress.
authors.affiliation: Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi.
authors.forename: Lusha
authors.initials: L
authors.lastname: Xiang
authors.forename: Silu
authors.initials: S
authors.lastname: Lu
authors.forename: Peter N
authors.initials: PN
authors.lastname: Mittwede
authors.forename: John S
authors.initials: JS
authors.lastname: Clemmer
authors.forename: Robert L
authors.initials: RL
authors.lastname: Hester
mesh_terms: D000098:Acetophenones / Q000494:pharmacology*; D055371:Acute Lung Injury / Q000097:blood / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control*; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008168:Lung / Q000098:blood supply / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D009104:Multiple Trauma / Q000150:complications* / Q000201:enzymology; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D009765:Obesity / Q000150:complications* / Q000201:enzymology; D018384:Oxidative Stress / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D011654:Pulmonary Edema / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control; D051381:Rats; D011924:Rats, Zucker; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D000098:Acetophenones; D004791:Enzyme Inhibitors; D018836:Inflammation Mediators; D015850:Interleukin-6; D009569:Nitric Oxide; C056165:acetovanillone; D009195:Peroxidase; D019255:NADPH Oxidases
keywords: and vascular permeability; lung injury; obesity; reactive oxygen species; trauma