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

• Published in: International immunopharmacology 2019-10, Vol.75, p.105735-105735, Article 105735
• Main Authors: Cerqueira, Jéssica Vieira, Meira, Cássio Santana, Santos, Emanuelle de Souza, de Aragão França, Luciana Souza, Vasconcelos, Juliana Fraga, Nonaka, Carolina Kymie Vasques, de Melo, Tarcísio Luna, dos Santos Filho, José Maurício, Moreira, Diogo Rodrigo Magalhães, Soares, Milena Botelho Pereira
• Format: Article
• Language: English
• Subjects: Allergens; Allergic airway inflammation; Allergic diseases; Alveoli; Animal models; Animals; Anti-Asthmatic Agents - therapeutic use; Anti-inflammatory agents; Anti-Inflammatory Agents - therapeutic use; Asthma; Asthma - drug therapy; Asthma - immunology; Asthma - pathology; Bronchoalveolar Lavage Fluid - immunology; Bronchus; Cytokines; Cytokines - immunology; Dexamethasone; Disease Models, Animal; Drugs; Eosinophils; Gene expression; Glucocorticoids; Hydrazones - therapeutic use; Immunoglobulin E; Immunosuppressive agents; Inflammatory diseases; Interleukin 10; Interleukin 13; Interleukin 4; Interleukin 5; Leukocyte Count; Leukocytes; Leukocytes (eosinophilic); Lung - drug effects; Lung - immunology; Lung - pathology; Lungs; Lymphocytes T; Male; Medical treatment; Mice, Inbred BALB C; Mucus; Mucus - immunology; N-acylhydraze; Ovalbumin; Respiratory tract; Respiratory tract diseases; Signs and symptoms
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2019.105735

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. •SintMed65 reduced cellularity and the number of eosinophils in bronchoalveolar fluid.•SintMed65 reduced the Th2 cytokines in bronchoalveolar fluid.•SintMed65 reduced the number of leukocytes and mucus production in lungs.•SintMed65 possesses a potent anti-inflammatory activity.