Pyroptosis and necroptosis inhibitor necrosulfonamide ameliorates lipopolysaccharide-induced inflammatory hyperalgesia in mice
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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Pensoft Publishers
2023-11-01
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| Series: | Pharmacia |
| Online Access: | https://pharmacia.pensoft.net/article/108995/download/pdf/ |
| _version_ | 1797596267790991360 |
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| author | Beyza Ozgen Sefika Pinar Senol Dilsah Ezgi Yilmaz Meryem Temiz-Resitoglu Omer Bahceli Bahar Tunctan |
| author_facet | Beyza Ozgen Sefika Pinar Senol Dilsah Ezgi Yilmaz Meryem Temiz-Resitoglu Omer Bahceli Bahar Tunctan |
| author_sort | Beyza Ozgen |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T02:48:07Z |
| format | Article |
| id | doaj.art-d3682546f2bc4a95a1924a6cfab0b36d |
| institution | Directory Open Access Journal |
| issn | 2603-557X |
| language | English |
| last_indexed | 2024-03-11T02:48:07Z |
| publishDate | 2023-11-01 |
| publisher | Pensoft Publishers |
| record_format | Article |
| series | Pharmacia |
| spelling | doaj.art-d3682546f2bc4a95a1924a6cfab0b36d2023-11-18T09:11:06ZengPensoft PublishersPharmacia2603-557X2023-11-017041345135410.3897/pharmacia.70.e108995108995Pyroptosis and necroptosis inhibitor necrosulfonamide ameliorates lipopolysaccharide-induced inflammatory hyperalgesia in miceBeyza Ozgen0Sefika Pinar Senol1Dilsah Ezgi Yilmaz2Meryem Temiz-Resitoglu3Omer Bahceli4Bahar Tunctan5Mersin UniversityTarsus UniversityMersin UniversityMersin UniversityMersin UniversityMersin UniversityObjectives: 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.https://pharmacia.pensoft.net/article/108995/download/pdf/ |
| spellingShingle | Beyza Ozgen Sefika Pinar Senol Dilsah Ezgi Yilmaz Meryem Temiz-Resitoglu Omer Bahceli Bahar Tunctan Pyroptosis and necroptosis inhibitor necrosulfonamide ameliorates lipopolysaccharide-induced inflammatory hyperalgesia in mice Pharmacia |
| title | Pyroptosis and necroptosis inhibitor necrosulfonamide ameliorates lipopolysaccharide-induced inflammatory hyperalgesia in mice |
| title_full | Pyroptosis and necroptosis inhibitor necrosulfonamide ameliorates lipopolysaccharide-induced inflammatory hyperalgesia in mice |
| title_fullStr | Pyroptosis and necroptosis inhibitor necrosulfonamide ameliorates lipopolysaccharide-induced inflammatory hyperalgesia in mice |
| title_full_unstemmed | Pyroptosis and necroptosis inhibitor necrosulfonamide ameliorates lipopolysaccharide-induced inflammatory hyperalgesia in mice |
| title_short | Pyroptosis and necroptosis inhibitor necrosulfonamide ameliorates lipopolysaccharide-induced inflammatory hyperalgesia in mice |
| title_sort | pyroptosis and necroptosis inhibitor necrosulfonamide ameliorates lipopolysaccharide induced inflammatory hyperalgesia in mice |
| url | https://pharmacia.pensoft.net/article/108995/download/pdf/ |
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