Effects of a Soluble Epoxide Hydrolase Inhibitor on Lipopolysaccharide-Induced Acute Lung Injury in Mice

• Published in: PloS one Vol. 11; no. 8; p. e0160359
• Main Authors: Tao, Wei, Li, Ping-Song, Yang, Liu-Qing, Ma, Yong-Bo
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 04.08.2016; Public Library of Science (PLoS)
• Subjects: Acute Lung Injury - chemically induced; Acute Lung Injury - drug therapy; Acute Lung Injury - enzymology; Analysis; Animal tissues; Animals; Biology and Life Sciences; Causes of; Chemokine CCL2 - metabolism; Complications and side effects; Dosage and administration; Drug therapy; Edema; Enzyme inhibitors; Enzyme Inhibitors - pharmacology; Epoxide hydrolase; Epoxide Hydrolases - antagonists & inhibitors; Epoxide Hydrolases - metabolism; Genetic aspects; Hydrolases; Hypertension; Inflammation; Inhibitors; Injuries; Kinases; Lipopolysaccharides; Lipopolysaccharides - toxicity; Lung diseases; Lungs; Male; Medicine and Health Sciences; Mice; Mice, Inbred BALB C; Monocyte chemoattractant protein; Neutrophils; Oxygenation; Pathogenesis; Permeability; Pharmacology; Phosphates; Physical Sciences; Physiological aspects; Plastic surgery; Pulmonary fibrosis; Research and Analysis Methods; Rodents; Sepsis; Staphylococcal enterotoxin H; Studies; Trachea; Trauma; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF; Tumor necrosis factor-α; China; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0160359

Inflammation plays a key role in the pathogenesis of acute lung injury (ALI). Soluble epoxide hydrolase (sEH) is suggested as a vital pharmacologic target for inflammation. In this study, we determined whether a sEH inhibitor, AUDA, exerts lung protection in lipopolysaccharide (LPS)-induced ALI in mice. Male BALB/c mice were randomized to receive AUDA or vehicle intraperitoneal injection 4 h after LPS or phosphate buffered saline (PBS) intratracheal instillation. Samples were harvested 24 h post LPS or PBS administration. AUDA administration decreased the pulmonary levels of monocyte chemoattractant protein (MCP)-1 and tumor necrosis factor (TNF)-α. Improvement of oxygenation and lung edema were observed in AUDA treated group. AUDA significantly inhibited sEH activity, and elevated epoxyeicosatrienoic acids (EETs) levels in lung tissues. Moreover, LPS induced the activation of nuclear factor (NF)-κB was markedly dampened in AUDA treated group. Administration of AUDA after the onset of LPS-induced ALI increased pulmonary levels of EETs, and ameliorated lung injury. sEH is a potential pharmacologic target for ALI.