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: Vinícius Rosa Oliveira, Mariana Barcellos Avila, Giovanna Marcella Cavalcante Carvalho, Sandra Maria F O Azevedo, Lidia Moreira Lima, Eliezer Jesus Barreiro, Alysson Roncally Carvalho, Walter Araujo Zin
• Journal: Toxicon : official journal of the International Society on Toxinology (Toxicon) Vol. 94 Pg. 29-35 (Feb 2015) ISSN: 1879-3150 [Electronic] England
• PMID: 25528385 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Alkaloids
• Anti-Inflammatory Agents
• Bacterial Toxins
• Cyanobacteria Toxins
• LASSBIO596
• Phthalic Acids
• Sulfonamides
• cylindrospermopsin
• Uracil

Topics

• Alkaloids
• Animals
• Anti-Inflammatory Agents (adverse effects, therapeutic use)
• Bacterial Toxins
• Cyanobacteria Toxins
• Lung Injury (chemically induced, drug therapy, pathology)
• Mice, Inbred BALB C
• Phthalic Acids (adverse effects, therapeutic use)
• Sulfonamides (adverse effects, therapeutic use)
• Survival Analysis
• Uracil (analogs & derivatives, toxicity)