Pyroptosis and necroptosis inhibitor necrosulfonamide ameliorates lipopolysaccharide-induced inflammatory hyperalgesia in mice

• Main Authors: Beyza Ozgen (Author), Sefika Pinar Senol (Author), Dilsah Ezgi Yilmaz (Author), Meryem Temiz-Resitoglu (Author), Omer Bahceli (Author), Bahar Tunctan (Author)
• Format: Book
• Published: Pensoft Publishers, 2023-11-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3897/pharmacia.70.e108995; 2603-557X
• Keywords: Pharmacy and materia medica; RS1-441
• Source: Pharmacia, Vol 70, Iss 4, Pp 1345-1354 (2023)

Objectives: This study aimed to investigate the effect of the gasdermin D (GSDMD) and mixed lineage kinase domain-like pseudokinase (MLKL) inhibitor, necrosulfonamide (NSA), on lipopolysaccharide (LPS)-induced hyperalgesia in mice. Methods: Reaction time to a thermal stimulus within 30 seconds was measured in male mice injected with saline, LPS, and/or NSA after 6 hours using the hot plate test. Immunoblotting studies were performed to determine changes in caspase-11/GSDMD-mediated pyroptosis, receptor-interacting serine/threonine-protein kinase (RIPK) 1/RIPK3/MLKL necrosome-mediated necroptosis, demyelination, and remyelination in the brains and spinal cords of animals. Results: NSA demonstrated significant antinociceptive activity compared with LPS-treated mice. In the tissues of LPS-treated mice, NSA decreased expression of caspase-11 p20, p30-GSDMD, interleukin-1β, high-mobility-group-box 1, and semaphorin 3A, and activity of RIPK1, RIPK3, and MLKL. NSA also increased the expression of myelin proteolipid protein. Conclusion: Therefore, NSA may have therapeutic potential in the treatment of inflammatory painful conditions due to bacterial infections.