Respiratory and Systemic Effects of LASSBio596 Plus Surfactant in Experimental Acute Respiratory Distress Syndrome.

Abstract

BACKGROUND/AIMS:

Exogenous surfactant has been proposed as adjunctive therapy for acute respiratory distress syndrome (ARDS), but it is inactivated by different factors present in the alveolar space. We hypothesized that co-administration of LASSBio596, a molecule with significant anti-inflammatory properties, and exogenous surfactant could reduce lung inflammation, thus enabling the surfactant to reduce edema and improve lung function, in experimental ARDS.

METHODS:

ARDS was induced by cecal ligation and puncture surgery in BALB/c mice. A sham-operated group was used as control (CTRL). After surgery (6 hours), CTRL and ARDS animals were assigned to receive: (1) sterile saline solution; (2) LASSBio596; (3) exogenous surfactant or (4) LASSBio596 plus exogenous surfactant (n = 22/group).

RESULTS:

Regardless of exogenous surfactant administration, LASSBio596 improved survival rate and reduced collagen fiber content, total number of cells and neutrophils in PLF and blood, cell apoptosis, protein content in BALF, and urea and creatinine levels. LASSBio596 plus surfactant yielded all of the aforementioned beneficial effects, as well as increased BALF lipid content and reduced surface tension.

CONCLUSION:

LASSBio596 exhibited major anti-inflammatory and anti-fibrogenic effects in experimental sepsis-induced ARDS. Its association with surfactant may provide further advantages, potentially by reducing surface tension.

• Authors: Johnatas Dutra Silva, Gisele Pena de Oliveira, Cynthia dos Santos Samary, Carla Cristina Araujo, Gisele de Araujo Padilha, Fernando Costa e Silva Filho, Rosilane Taveira da Silva, Marcelo Einicker-Lamas, Marcelo Marcos Morales, Vera Luiza Capelozzi, Vanessa Martins da Silva, Lídia Moreira Lima, Eliezer Jesus Barreiro, Bruno Lourenço Diaz, Paolo Pelosi, Pedro Leme Silva, Cristiane Souza Nascimento Baez Garcia, Patricia Rieken Macedo Rocco
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 38 Issue 2 Pg. 821-35 ( 2016) ISSN: 1421-9778 [Electronic] Germany
• PMID: 26905925 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 The Author(s) Published by S. Karger AG, Basel.

Chemical References

• Anti-Inflammatory Agents
• Biological Products
• LASSBIO596
• Phthalic Acids
• Pulmonary Surfactants
• Sulfonamides
• beractant

Topics

• Animals
• Anti-Inflammatory Agents (therapeutic use)
• Apoptosis (drug effects)
• Biological Products (therapeutic use)
• Lung (drug effects, immunology, pathology)
• Male
• Mice, Inbred BALB C
• Phthalic Acids (therapeutic use)
• Pulmonary Surfactants (therapeutic use)
• Respiratory Distress Syndrome (drug therapy, immunology, pathology)
• Sulfonamides (therapeutic use)
• Surface Tension (drug effects)