Coomassie brilliant blue G-250 dye attenuates bleomycin-induced lung fibrosis by regulating the NF-κB and NLRP3 crosstalk: A novel approach for filling an unmet medical need

Theodor Bilharz Research Institute

Bibliographic Information

Authors: Zohny M.H.; Cavalu S.; Youssef M.E.; Kaddah M.M.Y.; Mourad A.A.E.; Gaafar A.G.A.; El-Ahwany E.; Amin N.A.; Arakeep H.M.; Shata A.; Saleh S.; Hafez M.M.; Elazab S.T.; Abdelhady R.; El Shahat R.M.; Yahya G.; Saber S.

Journal: Biomedicine and Pharmacotherapy

Publisher: Elsevier Masson s.r.l.

Publication Date: April 2022

Volume / Issue: Volume 148

Article No.: 112723

ISSN: 7533322

DOI: 10.1016/j.biopha.2022.112723

Scopus: View on Scopus

PubMed: 35202914

Document Type: Article

Access: All Open Access; Gold Open Access; Green Open Access


Authors and Affiliations

Zohny M.H., Department of Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, 11152, Egypt; Cavalu S., Faculty of Medicine and Pharmacy, University of Oradea, P-ta 1 Decembrie 10, Oradea, 410087, Romania; Youssef M.E., Department of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, 11152, Egypt; Kaddah M.M.Y., Pharmaceutical and Fermentation Industries Development Center, City of Scientific Research and Technological Applications, Alexandria, New Borg El-Arab, 21934, Egypt; Mourad A.A.E., Department of Pharmacology and Toxicology, Faculty of Pharmacy, Port Said University, Port Said, 42511, Egypt; Gaafar A.G.A., Department of Pharmacology and Toxicology, Faculty of Pharmacy, Port Said University, Port Said, 42511, Egypt; El-Ahwany E., Department of Immunology, Theodor Bilharz Research Institute, Giza, Egypt; Amin N.A., Department of Haematology, Theodor Bilharz Research Institute, Giza, 12411, Egypt; Arakeep H.M., Department of Anatomy and Embryology, Faculty of Medicine, Tanta University, Tanta, Egypt; Shata A., Department of Clinical Pharmacology, Faculty of Medicine, Mansoura University, Mansoura, Egypt, Department of Clinical Pharmacy, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt; Saleh S., Department of Clinical Physiology, Faculty of Medicine, Menoufia University, Menoufia, Egypt; Hafez M.M., Department of Biochemistry, Faculty of Pharmacy, Ahram Canadian University, Giza, Egypt; Elazab S.T., Department of Pharmacology, Faculty of Veterinary medicine, Mansoura University, Mansoura, 35516, Egypt; Abdelhady R., Pharmacology and Toxicology Department, Faculty of Pharmacy, Fayoum University, Fayoum, Egypt; El Shahat R.M., Department of Pharmacology, Faculty of Medicine, Al-Azhar University, Cairo, 11884, Egypt; Yahya G., Department of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Al Sharqia, Egypt; Saber S., Department of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, 11152, Egypt


Abstract

Pulmonary fibrosis (PF) is a life-threatening disorder with a very poor prognosis. Because of the complexity of PF pathological mechanisms, filling such an unmet medical need is challenging. A number of pulmonary diseases have been linked to the activation of NF-κB and the NLRP3 inflammasome. Coomassie brilliant blue G-250 (CBBG) is proved to be a safe highly selective P2×7R antagonist with promising consequent inactivation of NLRP3 inflammasome. This is the first report to investigate the effect of CBBG on the bleomycin-induced lung fibrosis in rats. Our findings revealed that CBBG resulted in a significant improvement in histological features and oxidative status biomarkers of bleomycin-exposed lung tissue. Additionally, CBBG repressed collagen deposition as indicated after the analysis of hydroxyproline, TGF-β, PDGF-BB, TIMP-1, MMP-9, Col1a1, SMA and ICAM-1. It also exhibited anti-inflammatory potential as revealed by the determination of TNF-α, IL-1β, IL-18, MCP-1 in the lung tissue. In the bronchoalveolar lavage, the total protein and the LDH activity were substantially reduced. The lung protective effects of CBBG might be attributed on the one hand to the inhibition of NLRP3 inflammasome and on the other hand to the inactivation of NF-κB. Decreased levels of phospho-p65 and its DNA-binding activity as well as the analysis of TLR4 confirmed NF-κB inactivation. Caspase-1 activity is suppressed as a consequence of inhibiting NLRP3 inflammasome assembly. To conclude, CBBG may act as a primary or adjuvant therapy for the management of PF and therefore it may pose an opportunity for a novel approach to an unmet medical need. © 2022 The Authors


Keywords

Bleomycin; Coomassie brilliant blue G-250; Lung fibrosis; NF-κB; NLRP3; Animals; Inflammasomes; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Pulmonary Fibrosis; Rats; Rosaniline Dyes; alpha smooth muscle actin; biological marker; brilliant blue g; catalase; collagen type I alpha 1 chain; cryopyrin; gelatinase B; glutathione; hydroxyproline; immunoglobulin enhancer binding protein; intercellular adhesion molecule 1; interleukin 18; interleukin 1beta; interleukin 1beta converting enzyme; lactate dehydrogenase; malonaldehyde; platelet derived growth factor BB; secobarbital; superoxide dismutase; synaptotagmin I; thiopental; tissue inhibitor of metalloproteinase 1; toll like receptor 4; transforming growth factor beta; tumor necrosis factor; fuchsine; inflammasome; Nlrp3 protein, rat; adult; animal cell; animal experiment; animal model; animal tissue; antiinflammatory activity; Article; binding affinity; bronchoalveolar lavage fluid; cell infiltration; controlled study; DNA binding; enzyme activity; enzyme linked immunosorbent assay; histology; histopathology; lung lavage; male; nonhuman; oxidative stress; protein content; protein expression; rat; reverse transcription polymerase chain reaction; RNA extraction; scoring system; Sprague Dawley rat; unmet medical need; animal; metabolism


Citation Information

Scopus Citations: 44


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