title: BML-111, a lipoxin receptor agonist, attenuates ventilator-induced lung injury in rats.
abstract: Mechanical ventilation can cause structural and functional disturbances in the lung termed ventilator-induced lung injury (VILI). The aim of this study was to evaluate whether BML-111, a lipoxin receptor agonist, could attenuate VILI. Following induction of anesthesia and tracheostomy, Sprague-Dawley rats were ventilated with low tidal volume (6 mL/kg) or high tidal volume (20 mL/kg, HVT) for 4 h. Some rats subjected to HVT ventilation received BML-111 or vehicle (saline) by intraperitoneal injection. Some rats subjected to HVT and BML-111(1 mg/kg) received BOC-2 (a FPR2/ALX antagonist) intraperitoneally 30 min before BML-111. Sham rats were tracheotomized without ventilation. Treatment with BML-111 attenuated VILI, as evidenced by improved oxygenation and reduced histological injury compared with HVT-induced lung injury. BML-111 decreased indices of inflammation such as interleukin 1β, interleukin 6, tumor necrosis factor α, and bronchoalveolar lavage neutrophil infiltration. Administration with BML-111 suppressed the decrement of the nuclear factor κB (NF-κB) inhibitor IκB-α, diminished NF-κB activation, and reduced activation of mitogen-activated protein kinase in VILI. This study indicates that BML-111 attenuated VILI via a NF-κB and mitogen-activated protein kinase dependent mechanism. BML-111 may be a promising strategy for alleviation of VILI in patients subjected to mechanical ventilation.
authors.affiliation: Department of Critical Care Medicine, Institute of Anesthesia and Critical Care, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Hongbin
authors.initials: H
authors.lastname: Li
authors.forename: Zhouyang
authors.initials: Z
authors.lastname: Wu
authors.forename: Dan
authors.initials: D
authors.lastname: Feng
authors.forename: Jie
authors.initials: J
authors.lastname: Gong
authors.forename: Chengye
authors.initials: C
authors.lastname: Yao
authors.forename: Yaxin
authors.initials: Y
authors.lastname: Wang
authors.forename: Shiying
authors.initials: S
authors.lastname: Yuan
authors.forename: Shanglong
authors.initials: S
authors.lastname: Yao
authors.forename: You
authors.initials: Y
authors.lastname: Shang
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016207:Cytokines / Q000096:biosynthesis; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006538:Heptanoic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D020672:I-kappa B Proteins / Q000378:metabolism; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D044067:Receptors, Lipoxin / Q000819:agonists*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism; D014178:Translocation, Genetic / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects; D055397:Ventilator-Induced Lung Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*
chemical_list: C530770:5(S),6(R)-7-trihydroxyheptanoic acid, methyl ester; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D006538:Heptanoic Acids; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606206:Nfkbia protein, rat; D044067:Receptors, Lipoxin; C498145:Rela protein, rat; D018808:Transcription Factor AP-1; D051996:Transcription Factor RelA; D000072000:NF-KappaB Inhibitor alpha; D009195:Peroxidase; D020928:Mitogen-Activated Protein Kinases