title: Polyethylene glycol-conjugated superoxide dismutase attenuates septic lung injury in guinea pigs.
abstract: Reactive oxygen species (ROS), including superoxide anions, play an important role in mediating acute lung injury. We examined whether polyethylene glycol-conjugated superoxide dismutase (PEG-SOD) attenuates lung injury in Escherichia coli-treated guinea pigs. Twenty-four guinea pigs were divided into four groups: (1) control group; (2) septic group, in which live E. coli (2 x 10(9)/kg) were injected intravenously; (3) pretreatment group, in which PEG-SOD (2,000 IU/kg) was injected intravenously 15 min before E. coli; and (4) posttreatment group, in which PEG-SOD (2,000 IU/kg) was injected intravenously 30 min after E. coli. Lung injury was assessed by the concentration ratio of 125I-labeled albumin in lung tissue and bronchoalveolar lavage (BAL) fluid relative to plasma (L/P and BAL/P), lung wet-to-dry weight ratio, and the number of neutrophils in BAL fluid. Plasma half-life of PEG-SOD in normal guinea pigs was 13.5 h. L/P, lung wet-to-dry weight ratio, and the number of neutrophils in BAL fluid decreased in both pretreatment and posttreatment groups compared with the septic group. BAL/P decreased in the pretreatment group but not in the posttreatment group compared with the septic group. After the animal model studies, we investigated the effect of PEG-SOD on the human neutrophil extracellular generation of ROS stimulated by phorbol myristate acetate (PMA) in lucigenin-dependent chemiluminescence (CL). PEG-SOD at concentrations greater than or equal to 0.1 U/ml inhibited PMA-induced CL in a dose-dependent manner. We also examined the effect of PEG-SOD on the neutrophil intracellular generation of ROS using flow cytometry to assess intracellular hydroethidine oxidation.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Medicine, Stanford University Medical Center, California 94305-5236.
authors.forename: Y
authors.initials: Y
authors.lastname: Suzuki
authors.forename: T
authors.initials: T
authors.lastname: Tanigaki
authors.forename: D
authors.initials: D
authors.lastname: Heimer
authors.forename: W Z
authors.initials: WZ
authors.lastname: Wang
authors.forename: W G
authors.initials: WG
authors.lastname: Ross
authors.forename: H H
authors.initials: HH
authors.lastname: Sussman
authors.forename: T A
authors.initials: TA
authors.lastname: Raffin
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004927:Escherichia coli Infections / Q000150:complications; D005434:Flow Cytometry; D016166:Free Radical Scavengers; D006168:Guinea Pigs; D008163:Luminescent Measurements; D008168:Lung / Q000473:pathology; D009504:Neutrophils / Q000378:metabolism; D009929:Organ Size; D010100:Oxygen / Q000378:metabolism; D011092:Polyethylene Glycols / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012128:Respiratory Distress Syndrome / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D013482:Superoxide Dismutase / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D016166:Free Radical Scavengers; D011092:Polyethylene Glycols; D013482:Superoxide Dismutase; C063471:polyethylene glycol-superoxide dismutase; D010100:Oxygen