title: Apocynin attenuates ischemia-reperfusion lung injury in an isolated and perfused rat lung model.
abstract: Apocynin suppresses the generation of reactive oxygen species (ROS) that are implicated in ischemia-reperfusion (I/R) lung injury. We thus hypothesized that apocynin attenuates I/R. Furthermore, we explored the mechanisms by which apocynin may attenuate I/R. I/R was induced in an isolated and perfused rat lung model with ischemia for 1 h followed by reperfusion for 1 h. Apocynin was administered in the circulating perfusate at the onset of ischemia. Hemodynamics, lung injury indices, inflammatory responses, and activation of apoptotic pathways were determined. An increase in lung permeability and lung weight gain was noted after I/R. Peak airway pressure was increased, and pH of circulating perfusate was decreased. The adhesion molecule of neutrophil (CD31) in perfusate was upregulated. The levels of albumin, white blood cell count, and inflammatory cytokines including interleukin-1β, tumor necrosis factor-α, and macrophage inflammatory protein-2 increased in lung lavage fluid; the concentrations of carbonyl and thiobarbituric acid reactive substances were greater in the circulating perfusate; and the expression of myeloperoxidase, JNK, P38, and caspase-3 in lung tissue was greater in the control group. Upregulation and activation of nuclear factor-κB (NF-κB) in nuclei were found in I/R. The administration of apocynin attenuated these inflammatory responses and lung permeability associated with decreased activation of NF-κB. We conclude that I/R is associated with inflammatory responses including the generation of ROS, adhesion protein of neutrophil, cytokines, and the activation of mitogen-activated protein kinase and NF-κB cascade. The administration of apocynin attenuates the inflammatory responses and I/R in the isolated, perfused rat lung model.
authors.affiliation: Division of Pulmonary Immunology and Infectious Diseases, Chest Department, Taipei Veterans General Hospital, Taipei, Taiwan. chiang1990@gmail.com
authors.forename: Chi-Huei
authors.initials: CH
authors.lastname: Chiang
authors.forename: Chiao-Hui
authors.initials: CH
authors.lastname: Chuang
authors.forename: Shiou-Ling
authors.initials: SL
authors.lastname: Liu
mesh_terms: D000098:Acetophenones / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D015153:Blotting, Western; D004195:Disease Models, Animal; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000187:drug effects* / Q000473:pathology*; D008297:Male; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy*
chemical_list: D000098:Acetophenones; D000894:Anti-Inflammatory Agents, Non-Steroidal; C056165:acetovanillone; D009195:Peroxidase