Anti-inflammatory activity of SintMed65, an N-acylhydrazone derivative, in a mouse model of allergic airway inflammation.

Autor: Cerqueira JV; Instituto Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), CEP 40296-710 Salvador, BA, Brazil., Meira CS; Instituto Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), CEP 40296-710 Salvador, BA, Brazil., Santos ES; Instituto Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), CEP 40296-710 Salvador, BA, Brazil., de Aragão França LS; Centro de Biotecnologia e Terapia Celular, Hospital São Rafael, CEP 41253-190 Salvador, BA, Brazil., Vasconcelos JF; Instituto Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), CEP 40296-710 Salvador, BA, Brazil., Nonaka CKV; Centro de Biotecnologia e Terapia Celular, Hospital São Rafael, CEP 41253-190 Salvador, BA, Brazil., de Melo TL; Laboratório de Planejamento e Síntese Aplicados à Química Medicinal, Universidade Federal de Pernambuco, CEP: 50670-901 Recife, PE, Brazil., Dos Santos Filho JM; Laboratório de Planejamento e Síntese Aplicados à Química Medicinal, Universidade Federal de Pernambuco, CEP: 50670-901 Recife, PE, Brazil., Moreira DRM; Instituto Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), CEP 40296-710 Salvador, BA, Brazil., Soares MBP; Instituto Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), CEP 40296-710 Salvador, BA, Brazil. Electronic address: milena@bahia.fiocruz.br.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2019 Oct; Vol. 75, pp. 105735. Date of Electronic Publication: 2019 Jul 12.
DOI: 10.1016/j.intimp.2019.105735
Abstrakt: Asthma is a chronic, complex and heterogeneous inflammatory illness, characterized by obstruction of the lower airways. About 334 million people worldwide suffer from asthma, and these estimates, as well as the severity of the disease, have increased in the last decades. Glucocorticoids are currently the most widely used drugs in the treatment and control of asthma symptoms, but their prolonged use can cause serious adverse effects. N-acylhydrazone derivatives have been tested in pre-clinical studies in models of inflammatory diseases. Here we tested SintMed65 (N'-[(1E)-3-(4-nitrophenylhydrazono)]-(2E)-propan-2-ylidene-3,5-dinitrobenzohydrazide), a compound belonging to a novel class of immunosuppressive drugs, in a mouse model of allergic airway inflammation. BALB/c mice were sensitized previously and challenged with ovalbumin for five consecutive days and SintMed65 treatment was performed orally 1 h prior to challenge with ovalbumin. Administration of SintMed65, as well as the reference drug dexamethasone, reduced cellularity and the number of eosinophils in the bronchoalveolar fluid (BALF). SintMed65 also reduced the production of Th2 cytokines IL-4, IL-5 and IL-13 in the BALF, and IL-4, IL-10 and CCL8 gene expression in lung, compared to vehicle-treated mice. Importantly, a reduction in the number of leukocytes and in the mucus production in lungs of SintMed65-treated mice was found, compared to the vehicle-treated group. In contrast, IgE production was not significantly altered after treatment with SintMed65. Our results demonstrate that compound SintMed65 possesses anti-inflammatory characteristics, suggesting its therapeutic potential for the treatment of allergic diseases.
(Copyright © 2019 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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