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Toxicon. 2015 Feb;94:29-35. doi: 10.1016/j.toxicon.2014.12.004. Epub 2014 Dec 18.

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

Author information

1
Laboratory of Respiration Physiology, Carlos Chagas Filho Institute of Biophysics, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
2
Laboratory of Ecophysiology and Toxicology of Cyanobacteria, Carlos Chagas Filho Institute of Biophysics, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
3
Laboratory of Evaluation and Synthesis of Bioactive Substances (LASSBio(®)), Institute of Biomedical Sciences, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
4
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.

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.

KEYWORDS:

Cyanobacteria; Cylindrospermopsin; LASSBio-596; Lung mechanics; Pulmonary inflammation

PMID:
25528385
DOI:
10.1016/j.toxicon.2014.12.004
[Indexed for MEDLINE]

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