Remdesivir ameliorates ulcerative colitis-propelled cell inflammation and pyroptosis in acetic acid rats by restoring SIRT6/FoxC1 pathway
[Display omitted] •Induction of colitis in rats promotes oxidative, inflammatory, and pyroptotic events.•NLRP3/caspase 1/GSDMD is triggered in AA rats to initiate pyroptotic cell death.•Remdesivir enhanced SIRT6/FoxC1-mediated regulation of colonic inflammation.•Remdesivir ameliorated NLRP3/caspase...
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| Veröffentlicht in: | International immunopharmacology 2024-08, Vol.137, p.112465, Article 112465 |
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| creator | Oraby, Mamdouh A. Abdel Mageed, Sherif S. Amr Raouf, Ahmed Abdelshafy, Dareen A. Ahmed, Eman F. Khalil, Rowida T. Mangoura, Safwat A. Fadaly, Doaa S. |
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•Induction of colitis in rats promotes oxidative, inflammatory, and pyroptotic events.•NLRP3/caspase 1/GSDMD is triggered in AA rats to initiate pyroptotic cell death.•Remdesivir enhanced SIRT6/FoxC1-mediated regulation of colonic inflammation.•Remdesivir ameliorated NLRP3/caspase 1/GSDMD and thereby pyroptosis abrogation.
Ulcerative colitis (UC) is a primary culprit of inflammatory bowel disease that entails prompt and effective clinical intervention. Remdesivir (RDV), a broad-spectrum antiviral nucleotide, has been found to exert anti-inflammatory effects in experimental animals.
This study investigates the prospective anti-inflammatory merit of RDV on an experimental model of UC. The role of SIRT6/FoxC1 in regulating colonic cell inflammation and pyroptosis is delineated.
Rats were challenged with a single intrarectal dose of acetic acid (AA) solution (2 ml; 4 % v/v) to induce colitis. RDV (20 mg/kg, ip) and sulfasalazine (100 mg/kg, po) were administered to rats 14 days before the injection of AA.
Administration of RDV ameliorated colonic cell injury and loss as manifested by improvement of severe colon histopathological mutilation and macroscopic damage and disease activity index scores together with restoration of normal colon weight/length ratio. In addition, RDV alleviated colonic inflammatory reactions, thereby curtailing NF-κB activation and the inflammatory cytokines, TNF-α, IL-18, and IL-1β. Mitigation of colonic oxidative stress and apoptotic reactions were also evident in the setting of RDV treatment. Mechanistically, RDV enhanced the anti-inflammatory cascade, SIRT6/FoxC1, together with curbing the pyroptotic signal, NLRP3/cleaved caspase-1/Gasdermin D-elicited colonic inflammatory cell death.
This study reveals, for the first time, the anti-inflammatory effect of RDV against experimental UC. Augmenting SIRT6/FoxC1-mediated repression of colonic inflammation and pyroptosis might advocate the colo-protective potential of RDV. |
| doi_str_mv | 10.1016/j.intimp.2024.112465 |
| format | Article |
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•Induction of colitis in rats promotes oxidative, inflammatory, and pyroptotic events.•NLRP3/caspase 1/GSDMD is triggered in AA rats to initiate pyroptotic cell death.•Remdesivir enhanced SIRT6/FoxC1-mediated regulation of colonic inflammation.•Remdesivir ameliorated NLRP3/caspase 1/GSDMD and thereby pyroptosis abrogation.
Ulcerative colitis (UC) is a primary culprit of inflammatory bowel disease that entails prompt and effective clinical intervention. Remdesivir (RDV), a broad-spectrum antiviral nucleotide, has been found to exert anti-inflammatory effects in experimental animals.
This study investigates the prospective anti-inflammatory merit of RDV on an experimental model of UC. The role of SIRT6/FoxC1 in regulating colonic cell inflammation and pyroptosis is delineated.
Rats were challenged with a single intrarectal dose of acetic acid (AA) solution (2 ml; 4 % v/v) to induce colitis. RDV (20 mg/kg, ip) and sulfasalazine (100 mg/kg, po) were administered to rats 14 days before the injection of AA.
Administration of RDV ameliorated colonic cell injury and loss as manifested by improvement of severe colon histopathological mutilation and macroscopic damage and disease activity index scores together with restoration of normal colon weight/length ratio. In addition, RDV alleviated colonic inflammatory reactions, thereby curtailing NF-κB activation and the inflammatory cytokines, TNF-α, IL-18, and IL-1β. Mitigation of colonic oxidative stress and apoptotic reactions were also evident in the setting of RDV treatment. Mechanistically, RDV enhanced the anti-inflammatory cascade, SIRT6/FoxC1, together with curbing the pyroptotic signal, NLRP3/cleaved caspase-1/Gasdermin D-elicited colonic inflammatory cell death.
This study reveals, for the first time, the anti-inflammatory effect of RDV against experimental UC. Augmenting SIRT6/FoxC1-mediated repression of colonic inflammation and pyroptosis might advocate the colo-protective potential of RDV.</description><identifier>ISSN: 1567-5769</identifier><identifier>ISSN: 1878-1705</identifier><identifier>EISSN: 1878-1705</identifier><identifier>DOI: 10.1016/j.intimp.2024.112465</identifier><identifier>PMID: 38878489</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Acetic Acid ; Adenosine Monophosphate - analogs & derivatives ; Adenosine Monophosphate - pharmacology ; Adenosine Monophosphate - therapeutic use ; Alanine - analogs & derivatives ; Alanine - pharmacology ; Alanine - therapeutic use ; Animals ; Anti-Inflammatory Agents - pharmacology ; Anti-Inflammatory Agents - therapeutic use ; Colitis, Ulcerative - chemically induced ; Colitis, Ulcerative - drug therapy ; Colitis, Ulcerative - immunology ; Colitis, Ulcerative - pathology ; Colon - drug effects ; Colon - immunology ; Colon - pathology ; Cytokines - metabolism ; Disease Models, Animal ; Guanosine Monophosphate ; Humans ; Inflammation ; Male ; Pyroptosis ; Pyroptosis - drug effects ; Rats ; Remdesivir ; Signal Transduction - drug effects ; SIRT6/FoxC1 ; Sirtuins - metabolism ; Ulcerative colitis</subject><ispartof>International immunopharmacology, 2024-08, Vol.137, p.112465, Article 112465</ispartof><rights>2024 Elsevier B.V.</rights><rights>Copyright © 2024 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c241t-a6a5ea396df13a26e041e982e4989e257cf031dd8eaa0d6f61ae550a9d0249763</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.intimp.2024.112465$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38878489$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Oraby, Mamdouh A.</creatorcontrib><creatorcontrib>Abdel Mageed, Sherif S.</creatorcontrib><creatorcontrib>Amr Raouf, Ahmed</creatorcontrib><creatorcontrib>Abdelshafy, Dareen A.</creatorcontrib><creatorcontrib>Ahmed, Eman F.</creatorcontrib><creatorcontrib>Khalil, Rowida T.</creatorcontrib><creatorcontrib>Mangoura, Safwat A.</creatorcontrib><creatorcontrib>Fadaly, Doaa S.</creatorcontrib><title>Remdesivir ameliorates ulcerative colitis-propelled cell inflammation and pyroptosis in acetic acid rats by restoring SIRT6/FoxC1 pathway</title><title>International immunopharmacology</title><addtitle>Int Immunopharmacol</addtitle><description>[Display omitted]
•Induction of colitis in rats promotes oxidative, inflammatory, and pyroptotic events.•NLRP3/caspase 1/GSDMD is triggered in AA rats to initiate pyroptotic cell death.•Remdesivir enhanced SIRT6/FoxC1-mediated regulation of colonic inflammation.•Remdesivir ameliorated NLRP3/caspase 1/GSDMD and thereby pyroptosis abrogation.
Ulcerative colitis (UC) is a primary culprit of inflammatory bowel disease that entails prompt and effective clinical intervention. Remdesivir (RDV), a broad-spectrum antiviral nucleotide, has been found to exert anti-inflammatory effects in experimental animals.
This study investigates the prospective anti-inflammatory merit of RDV on an experimental model of UC. The role of SIRT6/FoxC1 in regulating colonic cell inflammation and pyroptosis is delineated.
Rats were challenged with a single intrarectal dose of acetic acid (AA) solution (2 ml; 4 % v/v) to induce colitis. RDV (20 mg/kg, ip) and sulfasalazine (100 mg/kg, po) were administered to rats 14 days before the injection of AA.
Administration of RDV ameliorated colonic cell injury and loss as manifested by improvement of severe colon histopathological mutilation and macroscopic damage and disease activity index scores together with restoration of normal colon weight/length ratio. In addition, RDV alleviated colonic inflammatory reactions, thereby curtailing NF-κB activation and the inflammatory cytokines, TNF-α, IL-18, and IL-1β. Mitigation of colonic oxidative stress and apoptotic reactions were also evident in the setting of RDV treatment. Mechanistically, RDV enhanced the anti-inflammatory cascade, SIRT6/FoxC1, together with curbing the pyroptotic signal, NLRP3/cleaved caspase-1/Gasdermin D-elicited colonic inflammatory cell death.
This study reveals, for the first time, the anti-inflammatory effect of RDV against experimental UC. Augmenting SIRT6/FoxC1-mediated repression of colonic inflammation and pyroptosis might advocate the colo-protective potential of RDV.</description><subject>Acetic Acid</subject><subject>Adenosine Monophosphate - analogs & derivatives</subject><subject>Adenosine Monophosphate - pharmacology</subject><subject>Adenosine Monophosphate - therapeutic use</subject><subject>Alanine - analogs & derivatives</subject><subject>Alanine - pharmacology</subject><subject>Alanine - therapeutic use</subject><subject>Animals</subject><subject>Anti-Inflammatory Agents - pharmacology</subject><subject>Anti-Inflammatory Agents - therapeutic use</subject><subject>Colitis, Ulcerative - chemically induced</subject><subject>Colitis, Ulcerative - drug therapy</subject><subject>Colitis, Ulcerative - immunology</subject><subject>Colitis, Ulcerative - pathology</subject><subject>Colon - drug effects</subject><subject>Colon - immunology</subject><subject>Colon - pathology</subject><subject>Cytokines - metabolism</subject><subject>Disease Models, Animal</subject><subject>Guanosine Monophosphate</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Male</subject><subject>Pyroptosis</subject><subject>Pyroptosis - drug effects</subject><subject>Rats</subject><subject>Remdesivir</subject><subject>Signal Transduction - drug effects</subject><subject>SIRT6/FoxC1</subject><subject>Sirtuins - metabolism</subject><subject>Ulcerative colitis</subject><issn>1567-5769</issn><issn>1878-1705</issn><issn>1878-1705</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc9u1DAQxiMEoqXwBgj5yCVb24md-IKEVhQqVUIq5Wy59gRmlcTB9i7sI_DWzCptj5xmZP_mzzdfVb0VfCO40Je7Dc4Fp2UjuWw3QshWq2fVuei7vhYdV88pV7qrVafNWfUq5x3n9N6Kl9VZ0xPV9ua8-nsLU4CMB0zMTTBiTK5AZvvRA2V4AObjiAVzvaS4wDhCYJ4Cw3kY3TQRE2fm5sCWIwElZsz0x5yHgp4CBkaNMrs_sgS5xITzD_bt-vZOX17FP1vBFld-_nbH19WLwY0Z3jzEi-r71ae77Zf65uvn6-3Hm9rLVpTaaafANUaHQTROaiBFYHoJrekNSNX5gTcihB6c40EPWjhQijsT6Eym081F9X7tS3p-7WkjO2E-KXIzxH22Ddd9p6RUhtB2RX2KOScY7JJwculoBbcnE-zOribYkwl2NYHK3j1M2N9PEJ6KHq9OwIcVANJ5QEg2e4TZQ8AEvtgQ8f8T_gE05Z0U</recordid><startdate>20240820</startdate><enddate>20240820</enddate><creator>Oraby, Mamdouh A.</creator><creator>Abdel Mageed, Sherif S.</creator><creator>Amr Raouf, Ahmed</creator><creator>Abdelshafy, Dareen A.</creator><creator>Ahmed, Eman F.</creator><creator>Khalil, Rowida T.</creator><creator>Mangoura, Safwat A.</creator><creator>Fadaly, Doaa S.</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20240820</creationdate><title>Remdesivir ameliorates ulcerative colitis-propelled cell inflammation and pyroptosis in acetic acid rats by restoring SIRT6/FoxC1 pathway</title><author>Oraby, Mamdouh A. ; Abdel Mageed, Sherif S. ; Amr Raouf, Ahmed ; Abdelshafy, Dareen A. ; Ahmed, Eman F. ; Khalil, Rowida T. ; Mangoura, Safwat A. ; Fadaly, Doaa S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c241t-a6a5ea396df13a26e041e982e4989e257cf031dd8eaa0d6f61ae550a9d0249763</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Acetic Acid</topic><topic>Adenosine Monophosphate - analogs & derivatives</topic><topic>Adenosine Monophosphate - pharmacology</topic><topic>Adenosine Monophosphate - therapeutic use</topic><topic>Alanine - analogs & derivatives</topic><topic>Alanine - pharmacology</topic><topic>Alanine - therapeutic use</topic><topic>Animals</topic><topic>Anti-Inflammatory Agents - pharmacology</topic><topic>Anti-Inflammatory Agents - therapeutic use</topic><topic>Colitis, Ulcerative - chemically induced</topic><topic>Colitis, Ulcerative - drug therapy</topic><topic>Colitis, Ulcerative - immunology</topic><topic>Colitis, Ulcerative - pathology</topic><topic>Colon - drug effects</topic><topic>Colon - immunology</topic><topic>Colon - pathology</topic><topic>Cytokines - metabolism</topic><topic>Disease Models, Animal</topic><topic>Guanosine Monophosphate</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Male</topic><topic>Pyroptosis</topic><topic>Pyroptosis - drug effects</topic><topic>Rats</topic><topic>Remdesivir</topic><topic>Signal Transduction - drug effects</topic><topic>SIRT6/FoxC1</topic><topic>Sirtuins - metabolism</topic><topic>Ulcerative colitis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Oraby, Mamdouh A.</creatorcontrib><creatorcontrib>Abdel Mageed, Sherif S.</creatorcontrib><creatorcontrib>Amr Raouf, Ahmed</creatorcontrib><creatorcontrib>Abdelshafy, Dareen A.</creatorcontrib><creatorcontrib>Ahmed, Eman F.</creatorcontrib><creatorcontrib>Khalil, Rowida T.</creatorcontrib><creatorcontrib>Mangoura, Safwat A.</creatorcontrib><creatorcontrib>Fadaly, Doaa S.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>International immunopharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Oraby, Mamdouh A.</au><au>Abdel Mageed, Sherif S.</au><au>Amr Raouf, Ahmed</au><au>Abdelshafy, Dareen A.</au><au>Ahmed, Eman F.</au><au>Khalil, Rowida T.</au><au>Mangoura, Safwat A.</au><au>Fadaly, Doaa S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Remdesivir ameliorates ulcerative colitis-propelled cell inflammation and pyroptosis in acetic acid rats by restoring SIRT6/FoxC1 pathway</atitle><jtitle>International immunopharmacology</jtitle><addtitle>Int Immunopharmacol</addtitle><date>2024-08-20</date><risdate>2024</risdate><volume>137</volume><spage>112465</spage><pages>112465-</pages><artnum>112465</artnum><issn>1567-5769</issn><issn>1878-1705</issn><eissn>1878-1705</eissn><abstract>[Display omitted]
•Induction of colitis in rats promotes oxidative, inflammatory, and pyroptotic events.•NLRP3/caspase 1/GSDMD is triggered in AA rats to initiate pyroptotic cell death.•Remdesivir enhanced SIRT6/FoxC1-mediated regulation of colonic inflammation.•Remdesivir ameliorated NLRP3/caspase 1/GSDMD and thereby pyroptosis abrogation.
Ulcerative colitis (UC) is a primary culprit of inflammatory bowel disease that entails prompt and effective clinical intervention. Remdesivir (RDV), a broad-spectrum antiviral nucleotide, has been found to exert anti-inflammatory effects in experimental animals.
This study investigates the prospective anti-inflammatory merit of RDV on an experimental model of UC. The role of SIRT6/FoxC1 in regulating colonic cell inflammation and pyroptosis is delineated.
Rats were challenged with a single intrarectal dose of acetic acid (AA) solution (2 ml; 4 % v/v) to induce colitis. RDV (20 mg/kg, ip) and sulfasalazine (100 mg/kg, po) were administered to rats 14 days before the injection of AA.
Administration of RDV ameliorated colonic cell injury and loss as manifested by improvement of severe colon histopathological mutilation and macroscopic damage and disease activity index scores together with restoration of normal colon weight/length ratio. In addition, RDV alleviated colonic inflammatory reactions, thereby curtailing NF-κB activation and the inflammatory cytokines, TNF-α, IL-18, and IL-1β. Mitigation of colonic oxidative stress and apoptotic reactions were also evident in the setting of RDV treatment. Mechanistically, RDV enhanced the anti-inflammatory cascade, SIRT6/FoxC1, together with curbing the pyroptotic signal, NLRP3/cleaved caspase-1/Gasdermin D-elicited colonic inflammatory cell death.
This study reveals, for the first time, the anti-inflammatory effect of RDV against experimental UC. Augmenting SIRT6/FoxC1-mediated repression of colonic inflammation and pyroptosis might advocate the colo-protective potential of RDV.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>38878489</pmid><doi>10.1016/j.intimp.2024.112465</doi></addata></record> |
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| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Acetic Acid Adenosine Monophosphate - analogs & derivatives Adenosine Monophosphate - pharmacology Adenosine Monophosphate - therapeutic use Alanine - analogs & derivatives Alanine - pharmacology Alanine - therapeutic use Animals Anti-Inflammatory Agents - pharmacology Anti-Inflammatory Agents - therapeutic use Colitis, Ulcerative - chemically induced Colitis, Ulcerative - drug therapy Colitis, Ulcerative - immunology Colitis, Ulcerative - pathology Colon - drug effects Colon - immunology Colon - pathology Cytokines - metabolism Disease Models, Animal Guanosine Monophosphate Humans Inflammation Male Pyroptosis Pyroptosis - drug effects Rats Remdesivir Signal Transduction - drug effects SIRT6/FoxC1 Sirtuins - metabolism Ulcerative colitis |
| title | Remdesivir ameliorates ulcerative colitis-propelled cell inflammation and pyroptosis in acetic acid rats by restoring SIRT6/FoxC1 pathway |
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