title: Diethylcarbamazine attenuates LPS-induced acute lung injury in mice by apoptosis of inflammatory cells.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, CPqAM/FIOCRUZ, Brazil. Electronic address: ingridtavaresdelima@gmail.com.
authors.forename: Ingrid Tavares
authors.initials: IT
authors.lastname: Fragoso
authors.affiliation: Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, CPqAM/FIOCRUZ, Brazil.
authors.forename: Edlene Lima
authors.initials: EL
authors.lastname: Ribeiro
authors.affiliation: Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, CPqAM/FIOCRUZ, Brazil.
authors.forename: Fabiana Oliveira Dos Santos
authors.initials: FO
authors.lastname: Gomes
authors.affiliation: Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, CPqAM/FIOCRUZ, Brazil.
authors.forename: Mariana Aragão Matos
authors.initials: MA
authors.lastname: Donato
authors.affiliation: Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, CPqAM/FIOCRUZ, Brazil.
authors.forename: Amanda Karolina Soares
authors.initials: AK
authors.lastname: Silva
authors.affiliation: Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, CPqAM/FIOCRUZ, Brazil.
authors.forename: Amanda Costa O de
authors.initials: AC
authors.lastname: Oliveira
authors.affiliation: Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, CPqAM/FIOCRUZ, Brazil.
authors.forename: Shyrlene Meiry da Rocha
authors.initials: SM
authors.lastname: Araújo
authors.affiliation: Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, CPqAM/FIOCRUZ, Brazil.
authors.forename: Karla Patrícia Sousa
authors.initials: KP
authors.lastname: Barbosa
authors.affiliation: Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, CPqAM/FIOCRUZ, Brazil.
authors.forename: Laise Aline Martins
authors.initials: LA
authors.lastname: Santos
authors.affiliation: Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, CPqAM/FIOCRUZ, Brazil.
authors.forename: Christina Alves
authors.initials: CA
authors.lastname: Peixoto
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D004049:Diethylcarbamazine / Q000494:pharmacology / Q000627:therapeutic use*; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D000893:Anti-Inflammatory Agents; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D004049:Diethylcarbamazine
keywords: Acute lung injury; Apoptosis; Diethylcarbamazine; Lipopolysaccharide; Resolution