title: Diethylcarbamazine inhibits NF-κB activation in acute lung injury induced by carrageenan in mice.
abstract: Diethylcarbamazine citrate (DEC) is widely used to treat lymphatic filariasis and Tropical Pulmonary Eosinophilia. A number of studies have reported a possible role in the host immune system, but exactly how DEC exerts this effect is still unknown. The present study reports the effects of DEC pretreatment on NF-κB regulation using the pleurisy model induced by carrageenan. Swiss male mice (Mus musculus) were divided into four experimental groups: control (SAL); carrageenan (CAR); diethylcarbamazine (DEC) and curcumin (CUR). The animals were pretreated with DEC (50mg/kg, v.o), CUR (50mg/kg, i.p) or distilled water for three consecutive days before pleurisy. One way analysis of variance (ANOVA) was performed by Tukey post-hoc test, and values were considered statistically significant when p<0.05. DEC pretreatment reduced tissue damage and the production of inflammatory markers, such as NO, iNOS, PGE2, COX-2, and PARP induced by carrageenan. Similarly, a known inhibitor of NF-κB pathway (curcumin) was also able to reduce these parameters. Like curcumin, DEC prevents NF-κB activation by reducing NF-κB p65 phosphorylation and IκBα degradation. DEC prevented NF-κB activation via p38 MAPK, but did not interfere in the ERK pathway in this experimental model. However, further studies should be developed to confirm this hypothesis. These findings suggest that DEC could be a promising drug for inflammatory disorders, especially in pulmonary diseases such as Acute Lung Inflammation, due its high anti-inflammatory potential which prevents NF-κB activation.
authors.affiliation: Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, CPqAM/FIOCRUZ, Brazil. Electronic address: laisealine@gmail.com.
authors.forename: Laise Aline Martins
authors.initials: LA
authors.lastname: Santos
authors.affiliation: Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, CPqAM/FIOCRUZ, Brazil. Electronic address: edlenelimaribeiro@gmail.com.
authors.forename: Edlene Lima
authors.initials: EL
authors.lastname: Ribeiro
authors.affiliation: Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, CPqAM/FIOCRUZ, Brazil. Electronic address: karlapsb@gmail.com.
authors.forename: Karla Patrícia Sousa
authors.initials: KP
authors.lastname: Barbosa
authors.affiliation: Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, CPqAM/FIOCRUZ, Brazil. Electronic address: ingridtavaresfragoso@hotmail.com.
authors.forename: Ingrid Tavares
authors.initials: IT
authors.lastname: Fragoso
authors.affiliation: Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, CPqAM/FIOCRUZ, Brazil. Electronic address: gomes.bio@gmail.com.
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. Electronic address: maridonato@gmail.com.
authors.forename: Mariana Aragão Matos
authors.initials: MA
authors.lastname: Donato
authors.affiliation: Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, CPqAM/FIOCRUZ, Brazil. Electronic address: ssbruna@gmail.com.
authors.forename: Bruna Santos
authors.initials: BS
authors.lastname: Silva
authors.affiliation: Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, CPqAM/FIOCRUZ, Brazil. Electronic address: kls.amanda@gmail.com.
authors.forename: Amanda Karolina Soares
authors.initials: AK
authors.lastname: Silva
authors.affiliation: Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, CPqAM/FIOCRUZ, Brazil. Electronic address: surawanessa@gmail.com.
authors.forename: Sura Wanessa Santos
authors.initials: SW
authors.lastname: Rocha
authors.affiliation: Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, CPqAM/FIOCRUZ, Brazil. Electronic address: mariaeduarda.rfranca@gmail.com.
authors.forename: Maria Eduarda Rocha
authors.initials: ME
authors.lastname: França
authors.affiliation: Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, CPqAM/FIOCRUZ, Brazil. Electronic address: gabrielb.rodrigues@hotmail.com.
authors.forename: Gabriel Barros
authors.initials: GB
authors.lastname: Rodrigues
authors.affiliation: Departamento de Antibióticos, Centro de Ciências Biológicas, Universidade Federal de Pernambuco, Brazil. Electronic address: teresinha100@gmail.com.
authors.forename: Teresinha Gonçalves
authors.initials: TG
authors.lastname: Silva
authors.affiliation: Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, CPqAM/FIOCRUZ, Brazil. Electronic address: peixoto.christina@gmail.com.
authors.forename: Christina Alves
authors.initials: CA
authors.lastname: Peixoto
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D002351:Carrageenan / Q000633:toxicity; D003474:Curcumin / Q000008:administration & dosage; D004049:Diethylcarbamazine / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004605:Elephantiasis, Filarial / Q000188:drug therapy*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D010998:Pleurisy / Q000139:chemically induced / Q000188:drug therapy*; D011657:Pulmonary Eosinophilia / Q000188:drug therapy*; D015398:Signal Transduction / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D018836:Inflammation Mediators; D016328:NF-kappa B; D002351:Carrageenan; D048051:p38 Mitogen-Activated Protein Kinases; D003474:Curcumin; D004049:Diethylcarbamazine
keywords: Diethylcarbamazine; Mitogen-activated protein kinases; Nuclear transcription factor-κB; Pleurisy