2. Academic Validation
  3. 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

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

  • Biomed Pharmacother. 2022 Apr;148:112723. doi: 10.1016/j.biopha.2022.112723.
Mona H Zohny 1,  Simona Cavalu 2,  Mahmoud E Youssef 3,  Mohamed M Y Kaddah 4,  Ahmed A E Mourad 5,  Ahmed Gaafar Ahmed Gaafar 6,  Eman El-Ahwany 7,  Noha A Amin 8,  Heba M Arakeep 9,  Ahmed Shata 10,  Safaa Saleh 11,  Mohamed M Hafez 12,  Sara T Elazab 13,  Rasha Abdelhady 14,  Rehab Mohamed El Shahat 15,  Galal Yahya 16,  Sameh Saber 17
Affiliations

Affiliations

  • 1 Department of Biochemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa 11152, Egypt. Electronic address: [email protected].
  • 2 Faculty of Medicine and Pharmacy, University of Oradea, P-ta 1 Decembrie 10, 410087 Oradea, Romania. Electronic address: [email protected].
  • 3 Department of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa 11152, Egypt. Electronic address: [email protected].
  • 4 Pharmaceutical and Fermentation Industries Development Center, City of Scientific Research and Technological Applications, New Borg El-Arab 21934, Alexandria, Egypt. Electronic address: [email protected].
  • 5 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Port Said University, Port Said 42511, Egypt. Electronic address: [email protected].
  • 6 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Port Said University, Port Said 42511, Egypt. Electronic address: [email protected].
  • 7 Department of Immunology, Theodor Bilharz Research Institute, Giza, Egypt. Electronic address: [email protected].
  • 8 Department of Haematology, Theodor Bilharz Research Institute, Giza 12411, Egypt. Electronic address: [email protected].
  • 9 Department of Anatomy and Embryology, Faculty of Medicine, Tanta University, Tanta, Egypt. Electronic address: [email protected].
  • 10 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. Electronic address: [email protected].
  • 11 Department of Clinical Physiology, Faculty of Medicine, Menoufia University, Menoufia, Egypt. Electronic address: [email protected].
  • 12 Department of Biochemistry, Faculty of Pharmacy, Ahram Canadian University, Giza, Egypt. Electronic address: [email protected].
  • 13 Department of Pharmacology, Faculty of Veterinary medicine, Mansoura University, Mansoura 35516, Egypt. Electronic address: [email protected].
  • 14 Pharmacology and Toxicology Department, Faculty of Pharmacy, Fayoum University, Fayoum, Egypt. Electronic address: [email protected].
  • 15 Department of Pharmacology, Faculty of Medicine, Al-Azhar University, Cairo 11884, Egypt. Electronic address: [email protected].
  • 16 Department of Microbiology and Immunology, Faculty of Pharmacy, Zagazig University, Al Sharqia, Egypt. Electronic address: [email protected].
  • 17 Department of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa 11152, Egypt. Electronic address: [email protected].
PMID: 35202914 DOI: 10.1016/j.biopha.2022.112723
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.

Keywords

Bleomycin; Coomassie brilliant blue G-250; Lung fibrosis; NF-κB; NLRP3.

Figures
Products