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. In this study, we established a mouse model of lipopolysaccharide (LPS)-induced inflammatory lung injury and investigated the effect of valnemulin (100 mg/kg) on acute lung injury (ALI) 8 h 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 pre-administration 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. In addition, valnemulin also inhibits the production of tumor necrosis factor-alpha, interleukin-6, and interleukin-1beta, which is consistent with mRNA expression in lung. The results showed that valnemulin had a protective effect on LPS-induced ALI in mice.
Chen
Zhibao
Z
Department of Veterinary Pharmacology, College of Animal Science and Veterinary Medicine, Jilin University, Changchun, Jilin 130062, People's Republic of China.
Zhang
Xuemei
X
Chu
Xiao
X
Zhang
Xiaozhe
X
Song
Keji
K
Jiang
Youshuai
Y
Yu
Lu
L
Deng
Xuming
X
D055371:Acute Lung Injury / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000276:immunology; D004195:Disease Models, Animal; D004224:Diterpenes / Q000494:pharmacology; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D004224:Diterpenes; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C482199:lipopolysaccharide, E coli O55-B5; C117845:valnemulin; D009195:Peroxidase; D013482:Superoxide Dismutase