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: Hongbin Li, Zhouyang Wu, Dan Feng, Jie Gong, Chengye Yao, Yaxin Wang, Shiying Yuan, Shanglong Yao, You Shang
• Journal: Shock (Augusta, Ga.) (Shock) Vol. 41 Issue 4 Pg. 311-6 (Apr 2014) ISSN: 1540-0514 [Electronic] United States
• PMID: 24365886 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 5(S),6(R)-7-trihydroxyheptanoic acid, methyl ester
• Anti-Inflammatory Agents, Non-Steroidal
• Cytokines
• Heptanoic Acids
• I-kappa B Proteins
• NF-kappa B
• Nfkbia protein, rat
• Receptors, Lipoxin
• Rela protein, rat
• Transcription Factor AP-1
• Transcription Factor RelA
• NF-KappaB Inhibitor alpha
• Peroxidase
• Mitogen-Activated Protein Kinases

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology, therapeutic use)
• Bronchoalveolar Lavage Fluid (cytology)
• Cytokines (biosynthesis)
• Drug Evaluation, Preclinical (methods)
• Heptanoic Acids (pharmacology, therapeutic use)
• I-kappa B Proteins (metabolism)
• Male
• Mitogen-Activated Protein Kinases (metabolism)
• NF-KappaB Inhibitor alpha
• NF-kappa B (metabolism)
• Peroxidase (metabolism)
• Phosphorylation
• Rats
• Rats, Sprague-Dawley
• Receptors, Lipoxin (agonists)
• Transcription Factor AP-1 (metabolism)
• Transcription Factor RelA (genetics, metabolism)
• Translocation, Genetic (drug effects)
• Up-Regulation (drug effects)
• Ventilator-Induced Lung Injury (metabolism, pathology, prevention & control)