Diethylcarbamazine attenuates LPS-induced acute lung injury in mice by apoptosis of inflammatory cells

Acute lung injury (ALI) is characterized by extensive neutrophil infiltration, and apoptosis delay considered part of the pathogenesis of the condition. Despite great advances in treatment strategies, few effective therapies are known for ALI. Diethylcarbamazine (DEC) is used against lymphatic filar...

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Bibliographic Details
Published in:	Pharmacological reports Vol. 69; no. 1; p. 81
Main Authors:	Fragoso, Ingrid Tavares, Ribeiro, Edlene Lima, Gomes, Fabiana Oliveira Dos Santos, Donato, Mariana Aragão Matos, Silva, Amanda Karolina Soares, Oliveira, Amanda Costa O de, Araújo, Shyrlene Meiry da Rocha, Barbosa, Karla Patrícia Sousa, Santos, Laise Aline Martins, Peixoto, Christina Alves
Format:	Journal Article
Language:	English
Published:	Switzerland 01-02-2017
Subjects:	Acute Lung Injury - chemically induced Acute Lung Injury - metabolism Acute Lung Injury - prevention & control Animals Anti-Inflammatory Agents - pharmacology Anti-Inflammatory Agents - therapeutic use Apoptosis - drug effects Apoptosis - physiology Diethylcarbamazine - pharmacology Diethylcarbamazine - therapeutic use Inflammation - chemically induced Inflammation - metabolism Inflammation - prevention & control Inflammation Mediators - antagonists & inhibitors Inflammation Mediators - metabolism Lipopolysaccharides - toxicity Male Mice Mice, Inbred C57BL Lipopolysaccharide Acute lung injury Diethylcarbamazine Apoptosis Resolution
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Summary:	Acute lung injury (ALI) is characterized by extensive neutrophil infiltration, and apoptosis delay considered part of the pathogenesis of the condition. Despite great advances in treatment strategies, few effective therapies are known for ALI. Diethylcarbamazine (DEC) is used against lymphatic filariasis, a number of studies have described its anti-inflammatory activities and pro-apoptotic effect. These properties have been associated with nuclear factor kappa-B inactivation. The aim of the present study was to investigate the effect of DEC on ALI induced by lipopolysaccharide (LPS) in mice. DEC effect was evaluated by histological and ultrastructural analysis, immunohistochemistry and western blot (WB). Also TUNEL assays were performed and as well as myeloperoxidase (MPO) levels and nitric oxide (NO) were measured. The results demonstrate that LPS induced histological and ultrastructural changes with tissue damage, intense cell infiltration and pulmonary edema, and also increased levels of MPO and NO. DEC reversed these effects, confirming its anti-inflammatory action. DEC pro-apoptotic activity was also evaluated. The expression of TUNEL-positive cells and caspase-3 was increased in DEC treated group. Furthermore, immunohistochemical and WB analysis showed that DEC increased the expression of pro-apoptotic proteins in both the intrinsic (Bax, cytochrome c and caspase-9) and the extrinsic pathways of apoptosis (Fas, FADD and caspase-8). Additionally, DEC reduced the expression of the anti-apoptotic protein Bcl-2. Our results suggest that DEC attenuates ALI through the prevention of inflammatory cells accumulation by stimulating apoptosis. DEC accelerates the resolution of inflammation and may be a potential pharmacological treatment for ALI.
ISSN:	1734-1140
DOI:	10.1016/j.pharep.2016.09.021