Unveiling the potential therapeutic role of nifuroxazide and liraglutide combination in mitigating LPS-induced acute lung injury through modulation of AT1R/JAK-2/STAT-3 by ACE2/ Ang1-7/MasR signaling in male albino rats: in vivo and in silico study
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View abstract on PubMed
Summary
This summary is machine-generated.This study shows that combining liraglutide and nifuroxazide effectively treats septic acute lung injury (S-ALI) in rats. The combination improved survival and reduced inflammation by modulating key signaling pathways.
Area Of Science
- Pharmacology and Toxicology
- Respiratory Medicine
- Molecular Biology
Background
- Septic acute lung injury (S-ALI) is a severe condition with high mortality.
- Current treatments for S-ALI have limitations, necessitating novel therapeutic strategies.
- The JAK2/STAT3/NFκB pathway and the ACE2/Ang1-7/MAS receptor axis are implicated in S-ALI pathogenesis.
Purpose Of The Study
- To investigate the therapeutic potential of combining liraglutide (LIR) and nifuroxazide (NIF) for S-ALI.
- To elucidate the underlying molecular mechanisms involving the JAK2/STAT3/NFκB and ACE2/Ang1-7/MAS pathways.
- To validate findings through molecular dynamic simulations and experimental studies.
Main Methods
- Animal model: Seventy-five male Wistar albino rats were used, divided into control, LPS-induced S-ALI, and treatment groups (ALI+NIF, ALI+LIR, ALI+LIR+NIF).
- Assessment of therapeutic effects: Survival rates, metabolic acidosis, inflammatory markers (IL-6, TNFα, iNOS, MPO, IL-1β), pulmonary edema, redox balance (SOD, catalase, GSH), histopathology, and protein/mRNA expression.
- Molecular dynamic simulations were employed to support experimental findings.
Main Results
- The LIR+NIF combination significantly improved 7-day survival rates and ameliorated metabolic acidosis in S-ALI rats.
- Combined treatment markedly reduced inflammatory responses and pulmonary leakage, restoring redox balance and improving histopathological scores.
- LIR+NIF downregulated JAK2/STAT3/NFκB signaling while upregulating the ACE2/Ang1-7/MAS axis and lung surfactant B expression.
Conclusions
- The combination of liraglutide and nifuroxazide demonstrates significant therapeutic efficacy in managing septic acute lung injury.
- This regimen modulates key inflammatory and protective signaling pathways, offering a promising novel treatment strategy for S-ALI.
- The study provides a comprehensive understanding of the combined therapeutic effects, supported by both experimental and computational approaches.
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