Protective effect of abamectin on acute lung injury induced by lipopolysaccharide in mice.
Abamectin, a broad-spectrum antiparasitic agent, has been shown to exert an anti-inflammatory effect, in vitro, by down regulating both the nuclear transcription factor kappa-B and the mitogen-activated protein kinase (MAPK) activation pathway. In this study, we investigated the role of abamectin in acute lung injury (ALI) induced by Lipopolysaccharide (LPS), and the invovment of MAPK and NF-κB. BALB/C mice were administered abamectin (PBS) orally, followed by a dose of 0.5 mg/kg of LPS. After 10 h, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in bronchoalveolar lavage fluid (BALF) were measured using enzyme-linked immunosorbent assay. The number of total cells, neutrophils, and macrophages in the BALF were determined. The right lung was then excised for histological examination and analysis of myeloperoxidase (MPO) activity. Phosphorylation of MAPK family and IκB were detected by western blot. We found that 2 mg/kg of abamectin had significant protective effects on ALI. Mice treated with LPS alone showed markedly increased TNF-α and IL-6 levels in the BALF. In addition, not only was the W/D ratio of lung tissue significantly decreased, the number of total cells, neutrophils and macrophages in the BALF was also significantly reduced 11 h after treatment with abamectin. Furthermore, p38MAPK, ERK, and IκB were activated in 10 h after LPS treatment, which could be blunted by Abamectin. These results indicate that abamectin could attenuate inflammatory injury induced by LPS through MAPK and NF-κB passway.
Institute of Zoonoses, College of Animal Science and Veterinary Medicine, Jilin University, Changchun, Jilin 130062, China.
Xiaozhe
X
Zhang
Jianhua
J
Li
Chi
C
Chen
Xinxin
X
Ci
Qinlei
Q
Yu
Xichen
X
Zhang
Xuming
X
Deng
D055371:Acute Lung Injury / Q000503:physiopathology / Q000517:prevention & control*; D000284:Administration, Oral; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid; D004797:Enzyme-Linked Immunosorbent Assay; D007249:Inflammation / Q000503:physiopathology / Q000517:prevention & control*; D015850:Interleukin-6 / Q000378:metabolism; D007559:Ivermectin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000633:toxicity; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C048324:abamectin; D007559:Ivermectin; D020928:Mitogen-Activated Protein Kinases