Abstract
Air pollution and environmental issues significantly impact life, resulting in the emergence and exacerbation of allergic asthma and other chronic respiratory infections. The main objective of this study is to suppress allergic asthma by TAK-242 from lipopolysaccharide-induced airway inflammation primarily stimulating toll-like receptor-4, and also to determine the potential mechanism of asthma eradication. The TAK-242 anti-allergic action was assured through the ovalbumin murine model of asthma via bronchial hyperresponsiveness and inflammation of the respiration tract in a pre-existing allergic inflammation paradigm. Swiss albino mice were sensitized and then challenged by ovalbumin and lipopolysaccharide for 5 days straight. TAK-242 reaction was assessed by inflammatory cytokines, and inflammatory cell count was determined from blood serum and bronchoalveolar lavage fluid, as well as group-wise regular weight assessments. After ovalbumin, lipopolysaccharide infusion, toll-like receptor-4 agonists caused a substantial increase in airway hyperresponsiveness, specific cellular inflammation, histological alterations, and immune mediator synthesis, as well as dose-related body-weight variations. A decrease in lipopolysaccharide-induced leukocyte count and Th1/Th17 related cytokines, TNF-α, and IL-6 expression through the ELISA study was particularly noticeable. Finally in treated groups, TAK-242, a TLR4/MD2 complex inhibitor, reduced airway inflammation and histopathological changes, cytokine expression, and body-weight management. TAK-242 has been found in an ovalbumin allergic asthma model to be a potential inhibitor of lipopolysaccharide-induced respiratory infection.
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All the interpreted data and materials used in this manuscript were generated during the experimental work investigation.
Abbreviations
- AHR:
-
Airway hyper-responsiveness
- BALF:
-
Broncho-alveolar lavage fluid
- CAT:
-
Catalase activity
- CD14:
-
Cluster of differentiation 14
- DEX:
-
Dexamethasone
- DLC:
-
Differential leukocyte count
- GPx:
-
Glutathione peroxidase
- GSH:
-
Reduced glutathione
- IL-1β:
-
Interleukin-1β
- LBP:
-
LPS binding protein
- LPS:
-
Lipopolysaccharide
- MDA:
-
Malondialdehyde
- MD2:
-
Myeloid differentiation protein-2
- NF-κB:
-
Nuclear factor-kappa B
- OVA:
-
Ovaalbumin
- TAK-242:
-
Resatorvid
- TLC:
-
Total leukocyte count
- TLRs:
-
Toll-like receptors
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The authors are grateful to Amity University, Noida, for internet access, journal access, and research supervision. We also thank R.V. Northland Institute of Pharmacy for giving the research facilities for the research study.
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Swamita Arora, Sangeetha Gupta, and Priti Tagde conceptualized the project; Swamita Arora and Wasim Akram prepared the initial manuscript; Swamita Arora and Sanjar Alam wrote the manuscript. Tanveer Naved and Priti Tagde reviewed and edited the manuscript. Swamita Arora helped in the experimentation. All authors reviewed and approved the work, and no print machine had been used because all data was generated in-house.
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Experimental research protocol work procedure has been done ethically, under general regulations and guidelines of the Experimental Animal Ethics Committee of the Department of Pharmacology, R.V. Northland Institute of Pharmacy, Chithera, Greater Noida, for the use and treatment of animals (ethical approval number: 1149/PO/Re/S/07/CPCSEA). Each author gave their full agreement and consent to fully participate throughout the writing of this manuscript.
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Arora, S., Tagde, P., Alam, S. et al. Influence of toll-like receptor-4 antagonist on bacterial load of asthma in Swiss albino mice: targeting TLR4/MD2 complex pathway. Environ Sci Pollut Res 30, 32854–32865 (2023). https://doi.org/10.1007/s11356-022-24521-4
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DOI: https://doi.org/10.1007/s11356-022-24521-4