title: Tempol, a membrane-permeable radical scavenger, ameliorates lipopolysaccharide-induced acute lung injury in mice: a key role for superoxide anion.
abstract: Acute lung injury or acute respiratory distress syndrome is a serious clinical problem with high mortality. Oxidative stress was found to play a major role in mediating lung injury and antioxidants have been shown to be effective in attenuating acute lung injury. In this study, we determine the effects of tempol, a membrane-permeable radical scavenger, in lipopolysaccharide (LPS)-induced acute lung injury and the underlying mechanism. Acute lung injury was induced by intraperitoneal injection of LPS (1mg/kg) and mice were treated with tempol 30min before injection of LPS. One hour later, bronchoalveolar lavage fluid was collected and subjected to estimation of total and differential cell counts as well as the proinflammatory cytokines; tumor necrosis factor-alpha(TNF-α), interleukin-1beta(IL-1β) and interferon-gamma (IFN-γ). Lung tissue damage was confirmed by histopathological changes and by immunohistochemical analysis of myeloperoxidase (MPO). Moreover, lipid peroxidation, reduced glutathione (GSH) and nitric oxide (NO) were investigated in the lung tissue. Pretreatment with tempol produced significant attenuation of LPS-induced lung injury as well as inhibition of LPS mediated increase in MPO immunostaining, MDA and NO levels in lung tissue. Elevated cytokines levels in both bronchoalveolar lavage fluid and lung tissue homogenates of acute lung injury mice were significantly decreased after administration of tempol. These findings confirmed significant protection by tempol against LPS-induced acute lung injury and that superoxide anion scavenging appears to be a potential target for new potential therapy in pulmonary disorders.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Egypt.
authors.forename: Nesrine S
authors.initials: NS
authors.lastname: El-Sayed
authors.forename: Laila G
authors.initials: LG
authors.lastname: Mahran
authors.forename: Mahmoud M
authors.initials: MM
authors.lastname: Khattab
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D002452:Cell Count; D002463:Cell Membrane Permeability; D003497:Cyclic N-Oxides / Q000378:metabolism* / Q000494:pharmacology* / Q000627:therapeutic use; D016207:Cytokines / Q000378:metabolism; D016166:Free Radical Scavengers / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D005978:Glutathione / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D013113:Spin Labels; D013481:Superoxides / Q000378:metabolism*
chemical_list: D003497:Cyclic N-Oxides; D016207:Cytokines; D016166:Free Radical Scavengers; D008070:Lipopolysaccharides; D013113:Spin Labels; D013481:Superoxides; D009569:Nitric Oxide; D008315:Malondialdehyde; D009195:Peroxidase; D005978:Glutathione; C001803:tempol