Investigating the therapeutic effects of LASSBio-596 in an in vivo model of cylindrospermopsin-induced lung injury

• Published in: Toxicon (Oxford) Vol. 94; pp. 29 - 35
• Main Authors: Oliveira, Vinícius Rosa, Avila, Mariana Barcellos, Carvalho, Giovanna Marcella Cavalcante, Azevedo, Sandra Maria F.O., Lima, Lidia Moreira, Barreiro, Eliezer Jesus, Carvalho, Alysson Roncally, Zin, Walter Araujo
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-02-2015
• Subjects: Animals; Anti-Inflammatory Agents - adverse effects; Anti-Inflammatory Agents - therapeutic use; Bacterial Toxins; Biocompatibility; Collapse; Cyanobacteria; Cylindrospermopsin; Exposure; Injuries; LASSBio-596; Lung Injury - chemically induced; Lung Injury - drug therapy; Lung Injury - pathology; Lung mechanics; Lungs; Mice; Mice, Inbred BALB C; Phthalic Acids - adverse effects; Phthalic Acids - therapeutic use; Pulmonary inflammation; Saline; Sulfonamides - adverse effects; Sulfonamides - therapeutic use; Survival; Survival Analysis; Uracil - analogs & derivatives; Uracil - toxicity; Pulmonary inflammation; LASSBio-596; Cyanobacteria; Cylindrospermopsin; Lung mechanics
• ISSN: 0041-0101; 1879-3150
• DOI: 10.1016/j.toxicon.2014.12.004

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.
•A murine model of cylindrospermopsin-induced lung injury was used.•LASSBio-596, an anti-inflammatory drug candidate, was tested.•LASSBio-596 ameliorated lung mechanics and histological alterations.•Lung inflammation was attenuated after treatment with LASSBio-596.•LASSBio-596 increased the survival rate of mice exposed to cylindrospermopsin.