Preventive Effect Of Abamectin On Acute Lung Injury Induced By Lipopolysaccharide In Mice

Abamectin is a member of macrolides, also called abamectin B1, which is afermentation product from a strain of Streptomyces avermitilis. It is reported thatabamectin has no anti-bacterium activity, so it can not be used as an antibiotic. It isextensively used against a broad spectrum of endoparasites and ectoparasites inanimals, and against different phytophagous pests of field crops, ornamentals,vegetables, and fruits and also used in controlling fire ants. In the process ofabamectin killing parasites, we find that some allergic symptoms induced by parasitehave been improved along the dying of parasite. So we assume that abamectin mayhave effect to the lung injury induced by lipopolysaccharide.Acute lung injury is a common respire system disease in clinic. The mostimportant one is endotoxemia induced by lipopolysaccharide which is thecomposition of Gram-negative bacteria. After lipopolysaccharide administration toanimals’ lung, a large amount of inflammation cells migrate from vascular toalveolar. At last, this process results to the overexpression of cytokines andrecruitment of macrophages, neutrophils and lymphocyte. Then lung injury will beshown.In this experiment, we investigated the role of abamectin in acute lung injury(ALI) induced by Lipopolysaccharide (LPS), and the invovment of MAPK andNF-κB. BALB/C mice were firstly administered abamectin (PBS) orally, followedby a dose of0.5mg/kg of LPS.10h later, mice were killed. Bronchoalveolar lavagefluid (BALF) was collected by intratracheal instillation followed by lavaging thelungs three times with0.5mL of sterile PBS. The cell pellet was suspended in PBSfor total cell, neutrophils and macrophage counts using cytospins by staining with awright‘s-giemsa’s stain method. And tumor necrosis factor-α (TNF-α) andinterleukin-6(IL-6) in BALF were measured using enzyme-linked immunosorbent assay. Mice treated with LPS alone showed markedly increased TNF-α and IL-6levels in the BALF. In addition, not only was the W/D ratio of lung tissuesignificantly decreased, the number of total cells, neutrophils and macrophages in the BALFwas also significantly reduced11h after treatment with abamectin. Meanwhile the activityof MPO in lung tissue also reduced after admistration of abamectin.Furthermore, we testified the activation of p38MAPK, ERK, and IκB. It wasreported that NF-κB and MAPK signaling pathway play an important role in theinflammation. NF-κB can modulate the expression cytokine, chemokine andadhesion. It would be activation after being stimulated by endotoxic or cytokines.MAPK is common in eukaryocyte. MAPK signaling pathway can stimulate genetranscription, protein synthesis, cell death and differentiation. This pathway containsthree core proteins: ERK1/2, p38and JNK.In this experiment, we found that abamectin could inhibit the activation ofNF-κB and MAPK signaling pathway, resulting to inhibit the expression of TNF-αand IL-6. But it just showed the protective effect of abamectin to acute lung injury inducedby LPS in the experiment, and could not suggested abamectin had effect in clinic.In conclusion, our results revealed the protective effects of abamectin in micewith LPS-induced ALI in the following ways: the inhibition of inflammatory cellsinfiltrating lung tissue, the reduction of pro-inflammatory cytokines’ production, andthe decrease in MPO activity. Meanwhile, histological examination also showed thatabamectin has significant anti-inflammatory activity during LPS-induced ALI.Therefore, these data strongly suggest that abamectin has potent anti-inflammatoryactions, and may represent a novel strategy for the modulation of inflammatoryresponse. Further more, we found that both NF-κB and p38MAPK werespontaneously activated during LPS attack and pretreatment of abamectin inhibitedthe degradation of IκB and the phosphorylation of p38MAPK. These resultssuggested that the inhibition of NF-κB activation by abamectin may be due toinhibition of p38MAPK and ERK phosphorylation.