title: A Plant Proteinase Inhibitor from Enterolobium contortisiliquum Attenuates Pulmonary Mechanics, Inflammation and Remodeling Induced by Elastase in Mice.
abstract: Proteinase inhibitors have been associated with anti-inflammatory and antioxidant activities and may represent a potential therapeutic treatment for emphysema. Our aim was to evaluate the effects of a plant Kunitz proteinase inhibitor,Enterolobium contortisiliquumtrypsin inhibitor (EcTI), on several aspects of experimental elastase-induced pulmonary inflammation in mice. C57/Bl6 mice were intratracheally administered elastase (ELA) or saline (SAL) and were treated intraperitoneally with EcTI (ELA-EcTI, SAL-EcTI) on days 1, 14 and 21. On day 28, pulmonary mechanics, exhaled nitric oxide (ENO) and number leucocytes in the bronchoalveolar lavage fluid (BALF) were evaluated. Subsequently, lung immunohistochemical staining was submitted to morphometry. EcTI treatment reduced responses of the mechanical respiratory system, number of cells in the BALF, and reduced tumor necrosis factor-α (TNF-α), matrix metalloproteinase-9 (MMP-9), matrix metalloproteinase-12 (MMP-12), tissue inhibitor of matrix metalloproteinase (TIMP-1), endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS)-positive cells and volume proportion of isoprostane, collagen and elastic fibers in the airways and alveolar walls compared with the ELA group. EcTI treatment reduced elastase induced pulmonary inflammation, remodeling, oxidative stress and mechanical alterations, suggesting that this inhibitor may be a potential therapeutic tool for chronic obstructive pulmonary disease (COPD) management.
authors.affiliation: Department of Clinical Medicine, School of Medicine, University of São Paulo, 01246-903 São Paulo, Brazil. osmartheodorojr@gmail.com.
authors.forename: Osmar Aparecido
authors.initials: OA
authors.lastname: Theodoro-Júnior
authors.affiliation: Department of Clinical Medicine, School of Medicine, University of São Paulo, 01246-903 São Paulo, Brazil. refragar@gmail.com.|Physical Therapy Department, Hospital Sírio-Libanês, 01308-050 São Paulo, Brazil. refragar@gmail.com.
authors.forename: Renato Fraga
authors.initials: RF
authors.lastname: Righetti
authors.affiliation: Department of Clinical Medicine, School of Medicine, University of São Paulo, 01246-903 São Paulo, Brazil. dosreisrafael@gmail.com.
authors.forename: Rafael
authors.initials: R
authors.lastname: Almeida-Reis
authors.affiliation: Department of Clinical Medicine, School of Medicine, University of São Paulo, 01246-903 São Paulo, Brazil. brunotad@gmail.com.
authors.forename: Bruno Tadeu
authors.initials: BT
authors.lastname: Martins-Oliveira
authors.affiliation: Department of Clinical Medicine, School of Medicine, University of São Paulo, 01246-903 São Paulo, Brazil. leandrooliva@hotmail.com.
authors.forename: Leandro Vilela
authors.initials: LV
authors.lastname: Oliva
authors.affiliation: Department of Bioscience, Federal University of Sao Paulo, 09972-270 Diadema, Brazil. cmaximoprado@gmail.com.
authors.forename: Carla Máximo
authors.initials: CM
authors.lastname: Prado
authors.affiliation: Department of Clinical Medicine, School of Medicine, University of São Paulo, 01246-903 São Paulo, Brazil. beatrizmsaraiva@gmail.com.
authors.forename: Beatriz Mangueira
authors.initials: BM
authors.lastname: Saraiva-Romanholo
authors.affiliation: Department of Clinical Medicine, School of Medicine, University of São Paulo, 01246-903 São Paulo, Brazil. leick51@yahoo.com.br.
authors.forename: Edna Aparecida
authors.initials: EA
authors.lastname: Leick
authors.affiliation: Department of Clinical Medicine, School of Medicine, University of São Paulo, 01246-903 São Paulo, Brazil. pinheiro.nathalia@gmail.com.
authors.forename: Nathalia Montouro
authors.initials: NM
authors.lastname: Pinheiro
authors.affiliation: Department of Biochemistry, Federal University of São Paulo, 09972-270 Diadema, Brazil. yara.lobo@yahoo.com.br.
authors.forename: Yara Aparecida
authors.initials: YA
authors.lastname: Lobo
authors.affiliation: Department of Clinical Medicine, School of Medicine, University of São Paulo, 01246-903 São Paulo, Brazil. mmartins@usp.br.
authors.forename: Mílton de Arruda
authors.initials: MA
authors.lastname: Martins
authors.affiliation: Department of Biochemistry, Federal University of São Paulo, 09972-270 Diadema, Brazil. olivamlv@gmail.com.
authors.forename: Maria Luiza Vilela
authors.initials: ML
authors.lastname: Oliva
authors.affiliation: Department of Clinical Medicine, School of Medicine, University of São Paulo, 01246-903 São Paulo, Brazil. iocalvo@uol.com.br.
authors.forename: Iolanda de Fátima Lopes Calvo
authors.initials: IF
authors.lastname: Tibério
mesh_terms: D056151:Airway Remodeling / Q000187:drug effects*; D000818:Animals; D015415:Biomarkers; D001992:Bronchoalveolar Lavage Fluid; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism; D007887:Fabaceae / Q000737:chemistry*; D008297:Male; D051379:Mice; D009077:Mucins / Q000096:biosynthesis; D018384:Oxidative Stress; D010196:Pancreatic Elastase / Q000378:metabolism*; D010936:Plant Extracts / Q000494:pharmacology*; D011014:Pneumonia / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D011480:Protease Inhibitors / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D009077:Mucins; D010936:Plant Extracts; D011480:Protease Inhibitors; D010196:Pancreatic Elastase
keywords: COPD; EcTI; emphysema; proteinase inhibitor