Preventive Effects Of Valnemulin On Lipopolysaccharide-induced Acute Lung Injury In Mice

Valnemulin reportedly regulates inflammatory responses in addition to its in vitro antibacterial activity. However, there is no information available about whether valnemulin could exert effect on inflammatory lung injury in vivo. In this study, we established a mouse model of LPS-induced inflammatory lung injury and investigated the effect of valnemulin (100 mg/kg) on acute lung injury (ALI) eight hours after LPS challenge. We prepared bronchoalveolar lavage fluid (BALF) for measuring protein concentrations, cytokine levels and superoxidase dismutase (SOD) activity, and collected lungs for assaying wet-to-dry weight (W/D) ratios, myeloperoxidase (MPO) activity, cytokine mRNA expression and histological change. We found that the preadministration of valnemulin significantly decreases the W/D ratio of lungs, protein concentrations and the number of total cells, neutrophils, macrophages and leukomonocytes, and histologic analysis indicates that valnemulin significantly attenuates tissue injury. Furthermore, valnemulin significantly increases LPS-induced SOD activity in BALF, and decreases lung MPO activity as well, consistent with its effects on neutrophil infiltration. In addition, valnemulin also inhibits the production of tumor necrosis factor-α(TNF-α), interleukin-6 (IL-6), and interleukin-1β(IL-1β), which is consistent with mRNA expression in lung. The results showed that valnemulin had a protective effect on LPS-induced ALI in mice.