title: Investigating the therapeutic effects of LASSBio-596 in an in vivo model of cylindrospermopsin-induced lung injury.
abstract: The cyanotoxin cylindrospermopsin (CYN) has lately been reported with a notorious toxicity to mammals. LASSBio-596 is a compound with anti-inflammatory actions. We aimed at evaluating the therapeutic effects of LASSBio-596 in a model of CYN-induced lung injury. Protocol #1: BALB/c mice received intratracheally (i.t.) 50-μL of saline or semi-purified extract of CYN (70 μg/kg). 18 h later, animals that received saline were gavaged with saline (SALSAL) or 50 mg/kg of LASSBio-596 (SALLAS), and mice that received CYN were gavaged with either saline (TOXSAL) or 50 mg/kg of LASSBio-596 (TOXLAS). Pulmonary mechanics was measured 6 h after gavage. Lungs were prepared for histology and inflammatory mediators determination. Protocol #2: Mice received 50-μL of CYN (70 μg/kg, i.t.) and 18 h later were gavaged with saline (NOT TREATED), or 50 mg/kg of LASSBio-596 (TREATED). Survival rates and pulmonary mechanics of the survivors were assessed. CYN exposure increased mechanical components, alveolar collapse, PMN cells and fiber deposition in the lungs, as well as the production of IL-1β, IL-6 and KC in Protocol #1. LASSBio-596 attenuated those changes. TREATED mice in Protocol #2 presented significantly higher survival rates and tended to improve lung mechanics. Briefly, LASSBio-596 showed positive effects in mice exposed to CYN.
authors.affiliation: Laboratory of Respiration Physiology, Carlos Chagas Filho Institute of Biophysics, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Vinícius Rosa
authors.initials: VR
authors.lastname: Oliveira
authors.affiliation: Laboratory of Respiration Physiology, Carlos Chagas Filho Institute of Biophysics, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Mariana Barcellos
authors.initials: MB
authors.lastname: Avila
authors.affiliation: Laboratory of Respiration Physiology, Carlos Chagas Filho Institute of Biophysics, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Giovanna Marcella Cavalcante
authors.initials: GM
authors.lastname: Carvalho
authors.affiliation: Laboratory of Ecophysiology and Toxicology of Cyanobacteria, Carlos Chagas Filho Institute of Biophysics, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Sandra Maria F O
authors.initials: SM
authors.lastname: Azevedo
authors.affiliation: Laboratory of Evaluation and Synthesis of Bioactive Substances (LASSBio(®)), Institute of Biomedical Sciences, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Lidia Moreira
authors.initials: LM
authors.lastname: Lima
authors.affiliation: Laboratory of Evaluation and Synthesis of Bioactive Substances (LASSBio(®)), Institute of Biomedical Sciences, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Eliezer Jesus
authors.initials: EJ
authors.lastname: Barreiro
authors.affiliation: Laboratory of Respiration Physiology, Carlos Chagas Filho Institute of Biophysics, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Alysson Roncally
authors.initials: AR
authors.lastname: Carvalho
authors.affiliation: Laboratory of Respiration Physiology, Carlos Chagas Filho Institute of Biophysics, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. Electronic address: wazin@biof.ufrj.br.
authors.forename: Walter Araujo
authors.initials: WA
authors.lastname: Zin
mesh_terms: D000470:Alkaloids; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001427:Bacterial Toxins; D000087522:Cyanobacteria Toxins; D055370:Lung Injury / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008807:Mice, Inbred BALB C; D010795:Phthalic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*; D016019:Survival Analysis; D014498:Uracil / Q000031:analogs & derivatives* / Q000633:toxicity
chemical_list: D000470:Alkaloids; D000893:Anti-Inflammatory Agents; D001427:Bacterial Toxins; D000087522:Cyanobacteria Toxins; C514420:LASSBIO596; D010795:Phthalic Acids; D013449:Sulfonamides; C089595:cylindrospermopsin; D014498:Uracil
keywords: Cyanobacteria; Cylindrospermopsin; LASSBio-596; Lung mechanics; Pulmonary inflammation