Author | Oliveira, Gisele P. | |
Author | SIlva, Johnatas D. | |
Author | Marques, Patricia S. | |
Author | Albuquerque, Cassiano Felippe Gonçalves de | |
Author | Santos, Heloísa L. | |
Author | Vasconcellos, Ana Paula | |
Author | Takiya, Christina M. | |
Author | Morales, Marcelo M. | |
Author | Pelosi, Paolo | |
Author | Mócsai, Attila | |
Author | Faria Neto, Hugo C. de Castro | |
Author | Rocco, Patricia R. M. | |
Access date | 2016-05-17T15:25:43Z | |
Available date | 2016-05-17T15:25:43Z | |
Document date | 2015 | |
Citation | OLIVEIRA, Gisele P. et al. The Effects of Dasatinib in Experimental Acute Respiratory Distress Syndrome Depend on Dose and Etiology. Cellular Physiology and Biochemistry, v.36, p.1644-1658, July 2015. | pt_BR |
ISSN | 1015-8987 | |
URI | https://www.arca.fiocruz.br/handle/icict/14317 | |
Language | eng | pt_BR |
Publisher | Karger | pt_BR |
Rights | open access | |
Subject in Portuguese | Síndrome da insuficiência respiratória aguda | pt_BR |
Title | The Effects of Dasatinib in Experimental Acute Respiratory Distress Syndrome Depend on Dose and Etiology | pt_BR |
Type | Article | |
DOI | 10.1159/000430325 | |
Abstract | Background/Aims: Evidence suggests that tyrosine-kinase inhibitors may attenuate lung
inflammation and fibrosis in experimental acute respiratory distress syndrome (ARDS). We
hypothesized that dasatinib, a tyrosine-kinase inhibitor, might act differently depending on
the ARDS etiology and the dose. Methods: C57/BL6 mice were divided to be pre-treated
with dasatinib (1mg/kg or 10mg/kg) or vehicle (1% dimethyl-sulfoxide) by oral gavage.
Thirty-minutes after pre-treatment, mice were subdivided into control (C) or ARDS groups.
ARDS animals received Escherichia coli lipopolysaccharide intratracheally (ARDSp) or
intraperitoneally (ARDSexp). A new dose of dasatinib or vehicle was administered at 6 and 24h.
Results: Forty-eight hours after ARDS induction, dasatinib 1mg/kg yielded: improved lung
morphofunction and reduced cells expressing toll-like receptor (TLR)-4 in lung, independent
of ARDS etiology; reduced neutrophil and levels of interleukin (IL)-6, IL-10 and transforming
growth factor (TGF)-β in ARDSp. The higher dose of dasatinib caused no changes in lung
mechanics, diffuse alveolar damage, neutrophil, or cells expressing TLR4, but increased IL-6,
vascular endothelial growth factor (VEGF), and cells expressing Fas receptor in lung in ARDSp.
In ARDSexp, it improved lung morphofunction, increased VEGF, and reduced cells expressing
TLR4. Conclusion: Dasatinib may have therapeutic potential in ARDS independent of etiology,
but careful dose monitoring is required. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho (IBCCF). Laboratório de Investigação Pulmonar. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho (IBCCF). Laboratório de Investigação Pulmonar. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho (IBCCF). Laboratório de Investigação Pulmonar. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho (IBCCF). Laboratório de Investigação Pulmonar. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho (IBCCF). Laboratório de Investigação Pulmonar. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho (IBCCF). Laboratório de Patologia Celular. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho (IBCCF). Laboratório de Fisiologia Celular e Molecular. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | University of Genoa. IRCCS San Martino IST. Department of Surgical Sciences and Integrated Diagnostics. Genoa, Italy. | pt_BR |
Affilliation | Semmelweis University School of Medicine. Departmento of Physiology. Budapest, Hungary. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunofarmacologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho (IBCCF). Laboratório de Investigação Pulmonar. Rio de Janeiro, RJ, Brasil. | pt_BR |
Subject | Dasatinib | pt_BR |
Subject | Cytokines | pt_BR |
Subject | Histology | pt_BR |
Subject | Lung mechanics | pt_BR |
Subject | Acute respiratory distress syndrome | pt_BR |
Subject | Toll like receptor-4 | pt_BR |
DeCS | Síndrome do Desconforto Respiratório do Adulto | pt_BR |
DeCS | Histologia | pt_BR |
DeCS | Citocinas | pt_BR |
DeCS | Dasatinibe | pt_BR |
e-ISSN | 1421-9778 | |