Abstract
We explored the effects of compound 33, a synthetic chalcone derivative with antioxidant activity, on lipopolysaccharide (LPS)-induced acute lung injury (ALI). Compound 33, dexamethasone or vehicle was administered intragastrically to mice 6 h before intratracheal instillation of LPS. After 24 h, the effects of compound 33 on alveolar structural damage were evaluated by assessing lung morphology and the wet/dry weight ratio. Protein and proinflammatory cytokine levels and superoxide dismutase activity were also examined in the cell free supernatant of bronchoalveolar lavage fluid. Additionally, we investigated the anti-inflammatory and antioxidant activity of compound 33 in vitro and its effects on the MAPK/NF-κB and Nrf2/HO-1 pathways. Pretreatment with compound 33 prevented LPS-induced structural damage, tissue edema, protein exudation, and overproduction of proinflammatory mediators. The effects of compound 33 were similar to or greater in magnitude than those of the positive control, dexamethasone. Moreover, compound 33 exerted anti-inflammatory and antioxidant effects in vitro by inhibiting the MAPK/NF-κB pathway and activating the Nrf2/HO-1 pathway. Compound 33 may therefore be a promising candidate treatment for ALI.
Highlights
Acute lung injury (ALI) manifests clinically as serious and acute respiratory dysfunction
Mean body weights were similar between the two groups (Figure 2A), indicating that compound 33 is realtively safe for use in mouse models
Compound 33 reduced wet weight (WW)/dry weight (DW) ratio by 34% and protein levels by 42%. These effects were slightly stronger than those observed for dex, which reduced WW/DW ratio by 27% and protein amounts by 40% (Figure 2D, 2E)
Summary
Acute lung injury (ALI) manifests clinically as serious and acute respiratory dysfunction. ALI has high morbidity and mortality rates, in the elderly [1]. The pathogenesis of ALI involves disruption of the alveolar capillary-epithelial barrier due to exaggerated pulmonary inflammation, increased permeability, and exudation of protein-rich serous fluid [2]. Oxidative damage and the resulting activation of multiple signaling pathways is associated with the pathogenesis of ALI [4]. Intratracheal administration of lipopolysaccharide (LPS), a pathogenic endotoxin found in the outer membrane of Gram-negative bacteria [5], induces pulmonary inflammation by enhancing the production of reactive oxygen species (ROS) and activating inflammatory responses. LPS is frequently used to induce ALI in animal models [6]
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