Abstract
ObjectivesInflammation 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.MethodsMale 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.ResultsAUDA 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.ConclusionAdministration 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.
Highlights
IntroductionInflammation plays a key role in the pathogenesis of acute lung injury (ALI) and its severe form acute respiratory distress syndrome (ARDS) [1]
AUDA administration decreased the pulmonary levels of monocyte chemoattractant protein (MCP)-1 and tumor necrosis factor (TNF)-α
LPS induced the activation of nuclear factor (NF)-κB was markedly dampened in AUDA treated group
Summary
Inflammation plays a key role in the pathogenesis of acute lung injury (ALI) and its severe form acute respiratory distress syndrome (ARDS) [1]. It is suggested that dysregulated and excessive inflammatory response may trigger a large number of activated inflammatory cells infiltrate in the lung and release cytokines, proteinases, and reactive oxygen species (ROS) [1, 2]. These factors enhance alveolar-capillary permeability, leading to exudation of the blood component into the alveolar space and pulmonary edema [3], resulting in refractory hypoxemia and high mortality which are the hallmark feature of ALI/ARDS [1]. Novel strategies for the treatment of ALI/ARDS are desirable
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
