Anti-asthmatic effect of nitric oxide metallo-donor FOR811A [cis-[Ru(bpy)2(2-MIM)(NO)](PF6)3] in the respiratory mechanics of Swiss mice.

Autor: Costa PPC; Department of Veterinary Clinics, Faculty of Veterinary, Federal University of Pelotas, Pelotas, RS, Brazil.; Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil., Waller SB; Department of Veterinary Clinics, Faculty of Veterinary, Federal University of Pelotas, Pelotas, RS, Brazil., Dos Santos GR; Laboratory of Biophysics of Respiration, Superior Institute of Biomedical Sciences, State University of Ceará, Fortaleza, CE, Brazil., Gondim FL; Laboratory of Biophysics of Respiration, Superior Institute of Biomedical Sciences, State University of Ceará, Fortaleza, CE, Brazil., Serra DS; Laboratory of Biophysics of Respiration, Superior Institute of Biomedical Sciences, State University of Ceará, Fortaleza, CE, Brazil., Cavalcante FSÁ; Laboratory of Biophysics of Respiration, Superior Institute of Biomedical Sciences, State University of Ceará, Fortaleza, CE, Brazil., Gouveia Júnior FS; Laboratory of Bioinorganic, Department of Organic and Inorganic Chemistry, Federal University of Ceará, Fortaleza, CE, Brazil., de Paula Júnior VF; Laboratory of Biotechnology and Molecular Biology, Superior Institute of Biomedical Sciences, State University of Ceará, Fortaleza, CE, Brazil., Sousa EHS; Laboratory of Bioinorganic, Department of Organic and Inorganic Chemistry, Federal University of Ceará, Fortaleza, CE, Brazil., Lopes LGF; Laboratory of Bioinorganic, Department of Organic and Inorganic Chemistry, Federal University of Ceará, Fortaleza, CE, Brazil., Ribeiro WLC; Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil., Monteiro HSA; Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2021 Mar 12; Vol. 16 (3), pp. e0248394. Date of Electronic Publication: 2021 Mar 12 (Print Publication: 2021).
DOI: 10.1371/journal.pone.0248394
Abstrakt: We aimed at evaluating the anti-asthmatic effect of cis-[Ru(bpy)2(2-MIM)(NO)](PF6)3 (FOR811A), a nitrosyl-ruthenium compound, in a murine model of allergic asthma. The anti-asthmatic effects were analyzed by measuring the mechanical lung and morphometrical parameters in female Swiss mice allocated in the following groups: untreated control (Ctl+Sal) and control treated with FOR811A (Ctl+FOR), along asthmatic groups untreated (Ast+Sal) and treated with FOR811A (Ast+FOR). The drug-protein interaction was evaluated by in-silico assay using molecular docking. The results showed that the use of FOR811A in experimental asthma (Ast+FOR) decreased the pressure-volume curve, hysteresis, tissue elastance, tissue resistance, and airway resistance, similar to the control groups (Ctl+Sal; Ctl+FOR). However, it differed from the untreated asthmatic group (Ast+Sal, p<0.05), indicating that FOR811A corrected the lung parenchyma and relaxed the smooth muscles of the bronchi. Similar to control groups (Ctl+Sal; Ctl+FOR), FOR811A increased the inspiratory capacity and static compliance in asthmatic animals (Ast+Sal, p<0.05), showing that this metallodrug improved the capacity of inspiration during asthma. The morphometric parameters showed that FOR811A decreased the alveolar collapse and kept the bronchoconstriction during asthma. Beyond that, the molecular docking using FOR811A showed a strong interaction in the distal portion of the heme group of the soluble guanylate cyclase, particularly with cysteine residue (Cys141). In summary, FOR811A relaxed bronchial smooth muscles and improved respiratory mechanics during asthma, providing a protective effect and promising use for the development of an anti-asthmatic drug.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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