title: Inhaled carbon monoxide and hyperoxic lung injury in rats.
abstract: Because carbon monoxide (CO) has been proposed to have anti-inflammatory properties, we sought protective effects of CO in pulmonary O(2) toxicity, which leads rapidly to lung inflammation and respiratory failure. Based on published studies, we hypothesized that CO protects the lung against O(2) by selectively increasing expression of antioxidant enzymes, thereby decreasing oxidative injury and inflammation. Rats exposed to O(2) with or without CO [50-500 parts/million (ppm)] for 60 h were compared for lung wet-to-dry weight ratio (W/D), pleural fluid volume, myeloperoxidase (MPO) activity, histology, expression of heme oxygenase-1 (HO-1), and manganese superoxide dismutase (Mn SOD) proteins. The brains were evaluated for histological evidence of damage from CO. In O(2)-exposed animals, lung W/D increased from 4.8 in normal rats to 6.3; however, only CO at 200 and 500 ppm decreased W/D significantly (to 5.9) during O(2) exposure. Large volumes of pleural fluid accumulated in all rats, with no significant CO treatment effect. Lung MPO values increased after O(2) and were not attenuated by CO treatment. CO did not enhance lung expression of oxidant-responsive proteins Mn SOD and HO-1. Animals receiving O(2) and CO at 200 or 500 ppm showed significant apoptotic cell death in the cortex and hippocampus by immunochemical staining. Thus significant protection by CO against O(2)-induced lung injury could not be confirmed in rats, even at CO concentrations associated with apoptosis in the brain.
authors.affiliation: Division of Pulmonary Medicine, Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: C E
authors.initials: CE
authors.lastname: Clayton
authors.forename: M S
authors.initials: MS
authors.lastname: Carraway
authors.forename: H B
authors.initials: HB
authors.lastname: Suliman
authors.forename: E D
authors.initials: ED
authors.lastname: Thalmann
authors.forename: K N
authors.initials: KN
authors.lastname: Thalmann
authors.forename: D E
authors.initials: DE
authors.lastname: Schmechel
authors.forename: C A
authors.initials: CA
authors.lastname: Piantadosi
mesh_terms: D000818:Animals; D001784:Blood Gas Analysis; D015153:Blotting, Western; D001927:Brain Diseases / Q000139:chemically induced / Q000378:metabolism; D002248:Carbon Monoxide / Q000494:pharmacology*; D002263:Carboxyhemoglobin / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000032:analysis / Q000378:metabolism; D051547:Heme Oxygenase-1; D018496:Hyperoxia / Q000378:metabolism*; D008168:Lung / Q000201:enzymology*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D010100:Oxygen / Q000097:blood / Q000633:toxicity; D010996:Pleural Effusion / Q000139:chemically induced / Q000378:metabolism; D011014:Pneumonia / Q000139:chemically induced / Q000378:metabolism; D011654:Pulmonary Edema / Q000139:chemically induced / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000032:analysis / Q000378:metabolism
chemical_list: D002248:Carbon Monoxide; D002263:Carboxyhemoglobin; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D013482:Superoxide Dismutase; D010100:Oxygen