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Small Immunomodulatory Molecules as Potential Therapeutics in Experimental Murine Models of Acute Lung Injury (ALI)/Acute Respiratory Distress Syndrome (ARDS)
Journal article   Open access   Peer reviewed

Small Immunomodulatory Molecules as Potential Therapeutics in Experimental Murine Models of Acute Lung Injury (ALI)/Acute Respiratory Distress Syndrome (ARDS)

Dilip Shah, Pragnya Das, Suchismita Acharya, Beamon Agarwal, Dale J Christensen, Stella M Robertson and Vineet Bhandari
International journal of molecular sciences, v 22(5), pp 1-20
04 Mar 2021
DOI: https://doi.org/10.3390/ijms22052573
PMID: 33806560
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.3390/ijms22052573View
Published, Version of Record (VoR)CC BY V4.0,  Open

Abstract

Acute Lung Injury - drug therapy Animals Chitin - pharmacology Disease Models, Animal Female Immunologic Factors - pharmacology Lipopolysaccharides - pharmacology Lung - drug effects Male Mice Mice, Inbred C57BL Pneumonia - drug therapy Pulmonary Edema - drug therapy Rats Rats, Sprague-Dawley Respiratory Distress Syndrome - drug therapy Sepsis - drug therapy Small Molecule Libraries - pharmacology
Acute lung injury (ALI) or its most advanced form, acute respiratory distress syndrome (ARDS) is a severe inflammatory pulmonary process triggered by a variety of insults including sepsis, viral or bacterial pneumonia, and mechanical ventilator-induced trauma. Currently, there are no effective therapies available for ARDS. We have recently reported that a novel small molecule AVR-25 derived from chitin molecule (a long-chain polymer of N-acetylglucosamine) showed anti-inflammatory effects in the lungs. The goal of this study was to determine the efficacy of two chitin-derived compounds, AVR-25 and AVR-48, in multiple mouse models of ALI/ARDS. We further determined the safety and pharmacokinetic (PK) profile of the lead compound AVR-48 in rats. ALI in mice was induced by intratracheal instillation of a single dose of lipopolysaccharide (LPS; 100 µg) for 24 h or exposed to hyperoxia (100% oxygen) for 48 h or undergoing cecal ligation and puncture (CLP) procedure and observation for 10 days. Both chitin derivatives, AVR-25 and AVR-48, showed decreased neutrophil recruitment and reduced inflammation in the lungs of ALI mice. Further, AVR-25 and AVR-48 mediated diminished lung inflammation was associated with reduced expression of lung adhesion molecules with improvement in pulmonary endothelial barrier function, pulmonary edema, and lung injury. Consistent with these results, CLP-induced sepsis mice treated with AVR-48 showed a significant increase in survival of the mice (80%) and improved lung histopathology in the treated CLP group. AVR-48, the lead chitin derivative compound, demonstrated a good safety profile. Both AVR-25 and AVR-48 demonstrate the potential to be developed as therapeutic agents to treat ALI/ARDS.

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13 Record Views
23 citations in Web of Science
19 citations in Scopus

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UN Sustainable Development Goals (SDGs)

This publication has contributed to the advancement of the following goals:

#3 Good Health and Well-Being

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Collaboration types
Domestic collaboration
Web of Science research areas
Biochemistry & Molecular Biology
Chemistry, Multidisciplinary
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