title: Modulatory potential of resveratrol during lung inflammatory disease.
abstract: Neutrophils are the first cells to achieve the sites of infection or inflammation in the lungs. The massive accumulation of these cells is associated with acute and chronic lung injury. Therefore, they have been implicated in the pathogenesis of many lung diseases through the release of reactive oxygen intermediates, proteolytic enzymes and Neutrophil Extracellular Traps (NETs). The excessive and continuous release of NETs, fibers composed by decondensed chromatin coated with neutrophil proteins, are associated to the impairment of lung function in different pathological settings. Flavonoids inhibit the respiratory burst of neutrophils in mammals. However, one of these flavonoids, resveratrol has a particular chemical property. It reduce Cu(II) to Cu(I) form with concomitant formation of reactive oxygen species, which can produce DNA breakage as reported in several in vitro models. We hypothesize that direct resveratrol administration in lungs can cleave DNA in NETs, improving lung function during acute airway infections or chronic inflammatory lung diseases. If the hypothesis is correct, the control of NET formation can be used to reduce the inflammatory environment in lung after neutrophil stimuli. Additionally, the production of proinflammatory cytokines by neutrophils could be also diminished by resveratrol administration. In this sense, this flavonoid provides a multifaceted opportunity for treatment of lung diseases with strong or chronic neutrophil activation.
authors.affiliation: Centro INFANT - Pontifical Catholic University of Rio Grande do Sul - PUCRS, Porto Alegre, Brazil. Electronic address: josevargas123@gmail.com.
authors.forename: José Eduardo
authors.initials: JE
authors.lastname: Vargas
authors.affiliation: Department of Pure Chemistry, School of Chemistry, Pontifical Catholic University of Rio Grande do Sul - PUCRS, Porto Alegre, Brazil.
authors.forename: André Arigony
authors.initials: AA
authors.lastname: Souto
authors.affiliation: Centro INFANT - Pontifical Catholic University of Rio Grande do Sul - PUCRS, Porto Alegre, Brazil.
authors.forename: Paulo Márcio Condessa
authors.initials: PM
authors.lastname: Pitrez
authors.affiliation: Centro INFANT - Pontifical Catholic University of Rio Grande do Sul - PUCRS, Porto Alegre, Brazil.
authors.forename: Renato Tetelbom
authors.initials: RT
authors.lastname: Stein
authors.affiliation: Centro INFANT - Pontifical Catholic University of Rio Grande do Sul - PUCRS, Porto Alegre, Brazil.
authors.forename: Bárbara Nery
authors.initials: BN
authors.lastname: Porto
mesh_terms: D055371:Acute Lung Injury / Q000473:pathology; D000975:Antioxidants / Q000627:therapeutic use*; D002843:Chromatin / Q000378:metabolism; D004249:DNA Damage; D005419:Flavonoids / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008962:Models, Theoretical; D009504:Neutrophils / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012129:Respiratory Function Tests; D000077185:Resveratrol; D013267:Stilbenes / Q000627:therapeutic use*
chemical_list: D000975:Antioxidants; D002843:Chromatin; D005419:Flavonoids; D017382:Reactive Oxygen Species; D013267:Stilbenes; D000077185:Resveratrol