We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
The Effects of Dasatinib in Experimental Acute Respiratory Distress Syndrome Depend on Dose and Etiology.
- Authors
Oliveira, Gisele P.; Silva, Johnatas D.; Marques, Patricia S.; Gonçalves-de-albuquerque, Cassiano F.; Santos, Heloísa L.; Vascocellos, ana Paula; Takiya, Christina M.; Morales, Marcelo M.; Pelosi, Paolo; Mócsai, attila; de Castro-Faria-Neto, Hugo C.; Rocco, Patricia R.M.
- 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.
- Subjects
RESPIRATORY distress syndrome treatment; ETIOLOGY of diseases; DASATINIB; PROTEIN-tyrosine kinase inhibitors; INFLAMMATION; GENE expression; THERAPEUTICS
- Publication
Cellular Physiology & Biochemistry (Karger AG), 2015, Vol 36, Issue 4, p1644
- ISSN
1015-8987
- Publication type
Article
- DOI
10.1159/000430325