Academic Journal
Small Immunomodulatory Molecules as Potential Therapeutics in Experimental Murine Models of Acute Lung Injury (ALI)/Acute Respiratory Distress Syndrome (ARDS)
| Τίτλος: | Small Immunomodulatory Molecules as Potential Therapeutics in Experimental Murine Models of Acute Lung Injury (ALI)/Acute Respiratory Distress Syndrome (ARDS) |
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| Συγγραφείς: | Shah, Dilip, Das, Pragnya, Acharya, Suchismita, Agarwal, Beamon, Christensen, Dale J., Robertson, Stella M., Bhandari, Vineet |
| Πηγή: | International Journal of Molecular Sciences |
| Στοιχεία εκδότη: | MDPI |
| Έτος έκδοσης: | 2022 |
| Συλλογή: | UNTHSC Scholarly Repository (University. of North Texas Health Science Center) |
| Θεματικοί όροι: | Avr-25, Avr-48, acute lung injury, lung inflammation, pulmonary edema, sepsis, Acute Lung Injury / drug therapy, Animals, Chitin / pharmacology, Disease Models, Animal, Female, Immunologic Factors / pharmacology, Lipopolysaccharides / pharmacology, Lung / drug effects, Male, Mice, Inbred C57BL, Pneumonia / drug therapy, Pulmonary Edema / drug therapy, Rats, Sprague-Dawley, Respiratory Distress Syndrome / drug therapy, Sepsis / drug therapy, Small Molecule Libraries / pharmacology |
| Περιγραφή: | BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Both AVR-25 and AVR-48 demonstrate the potential to be developed as therapeutic agents to treat ALI/ARDS. ; This research was funded, in part, by a research contract received from AyuVis Research Inc. |
| Τύπος εγγράφου: | article in journal/newspaper |
| Περιγραφή αρχείου: | application/pdf |
| Γλώσσα: | unknown |
| Relation: | https://doi.org/10.3390/ijms22052573; Shah, D., Das, P., Acharya, S., Agarwal, B., Christensen, D. J., Robertson, S. M., & Bhandari, V. (2021). Small Immunomodulatory Molecules as Potential Therapeutics in Experimental Murine Models of Acute Lung Injury (ALI)/Acute Respiratory Distress Syndrome (ARDS). International journal of molecular sciences, 22(5), 2573. https://doi.org/10.3390/ijms22052573; https://hdl.handle.net/20.500.12503/31592; 22 |
| Διαθεσιμότητα: | https://hdl.handle.net/20.500.12503/31592 |
| Rights: | Attribution 4.0 International (CC BY 4.0) ; http://creativecommons.org/licenses/by/4.0/ ; © 2021 by the authors. |
| Αριθμός Καταχώρησης: | edsbas.256BDB8 |
| Βάση Δεδομένων: | BASE |
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