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Introduction
Acute lung injury (ALI) and the more severe acute respiratory distress syndrome (ARDS) are serious and potentially life-threatening events, which are characterized by pulmonary infiltrates, hypoxemia and edema (1). Despite tremendous advances in the prevention and treatment of ALI, the incidence of ALI is high and the mortality rate remains as high as 40% (2). Furthermore, the treatment of ALI represents an enormous financial burden to society and individuals. In addition, no effective therapeutic regimen is available for patients with this syndrome. Therefore, additional research is urgently required to explore novel pathways that may be targeted for the development of novel treatment options.
Although the pathophysiology of ALI has remained to be fully elucidated, an exaggerated inflammatory response has been reported to have a significant role (1). The inflammatory response is initiated, amplified and regulated by a complex network of cytokines and other pro-inflammatory cytokines (3). Pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and macrophage inflammatory protein 2 (MIP2) have been demonstrated to have a role in the pathogenesis of ALI (4). Exaggerated neutrophilic infiltration is responsible for the damage of alveolar-capillary barrier (5), resulting in the non-cardiogenic pulmonary edema. In addition, oxidative stress modulated by reactive oxygen species (ROS) is involved in the pathogenesis of ALI (6,7). Oxidative stress promotes the recruitment and activation of residential neutrophils and macrophages, leading to inflammatory and thereby cellular injury (8). Moreover, the phosphatidylinositide-3-kinase (PI3K)/AKT signaling pathway has been reported to negatively regulate lipopolysaccharide (LPS)-induced acute inflammatory responses in vitro and in vivo (9,10). Previous studies have found that inhibition of the PI3K/AKT signaling pathway exerts a protective role in ALI (11).
Naringenin, a flavonoid contained in citrus fruit, grapefruits and tomatoes, has been reported to exert multiple biological and pharmacological effects, such as anti-oxidative, anti-proliferative, anti-inflammatory and anti-tumor activities (12–15). Previous studies have suggested that naringenin protected normal human bronchial epithelium against LPS-induced injury (16) and improved LPS-induced ALI in rats through its anti-inflammatory, anti-oxidant, anti-nitrosative and anti-apoptotic effects (17). However, whether naringenin protects against LPS-induced ALI through the PI3K/AKT signaling pathway has remained to be investigated. Therefore, the present study explored the effects of naringenin on LPS-induced ALI, as well as the underlying signaling pathways.
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