Protective role of N-acetyl-l-tryptophan against hepatic ischemia-reperfusion injury via the RIP2/caspase-1/IL-1β signaling pathway
Context: Hepatic ischemia-reperfusion injury (HIRI) is a complex process observed during liver resection and transplantation. N-acetyl-l-tryptophan (l-NAT), an antagonist of neurokinin 1 receptor, has been used for the treatment of nausea and neurodegenerative diseases. Objective: This study investi...
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| Veröffentlicht in: | Pharmaceutical biology 2019-01, Vol.57 (1), p.385-391 |
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| creator | Wang, Jianxin Yu, Shuna Li, Jianguo Li, Huiting Jiang, Hongxin Xiao, Peilun Pan, Yitong Zheng, Jie Yu, Li Jiang, Jiying |
| description | Context: Hepatic ischemia-reperfusion injury (HIRI) is a complex process observed during liver resection and transplantation. N-acetyl-l-tryptophan (l-NAT), an antagonist of neurokinin 1 receptor, has been used for the treatment of nausea and neurodegenerative diseases.
Objective: This study investigates the protective effect of l-NAT against HIRI and explores the potential underlying mechanisms.
Materials and methods: Adult male Sprague-Dawley (SD) rats were randomly divided into three groups: sham, I/R and I/R + l-NAT. HIRI model was generated by clamping the hepatic artery, portal vein and common bile duct with a microvascular bulldog clamp for 45 min, and then removing the clamp and allowing reperfusion for 6 h. BRL cells were exposed to 200 µM H
2
O
2
with or without 10 µM l-NAT for 6 h.
Results: After l-NAT intervention, the structure of hepatic lobules was intact, and no swelling was noted in the cells. Furthermore, cell viability was found to be significantly enhanced when compared with the controls (p |
| doi_str_mv | 10.1080/13880209.2019.1617750 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_doaj_</sourceid><recordid>TN_cdi_proquest_miscellaneous_2245673819</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><doaj_id>oai_doaj_org_article_229e237879bc41e9af71bf72b8f470a7</doaj_id><sourcerecordid>2391267164</sourcerecordid><originalsourceid>FETCH-LOGICAL-c562t-9e707470ad9c788c4d893202447bd24beb0590bdbf235c5f1993d132ddb9313f3</originalsourceid><addsrcrecordid>eNp9ksuO0zAUhiMEYoaBRwBZYsMmrS9JbG8QaMSlUgUjBGvrxLFbV2kcbGdG2fNEPAjPhEs7I4YFK1v258_nHP1F8ZzgBcECLwkTAlMsFxQTuSAN4bzGD4pzwquqrAlpHuZ9ZsoDdFY8iXGHMa4Zqx8XZ4wQUUnWnBc_roJPRid3bVDwvUHeok8laJPmvuzLFOYx-XELA4INuCEmtDUjJKeRi3pr9g7KYEYT7BSdH5AbdlOY0bUDlLYGfVld0aWGOEI0JVmu1iX59RNFtxmgd8MGZdP2BuanxSMLfTTPTutF8e39u6-XH8v15w-ry7frUtcNTaU0HPOKY-ik5kLoqhOSUUyrircdrVrT4lritmstZbWuLZGSdYTRrmslI8yyi2J19HYedmoMbg9hVh6c-nPgw0ZByL31RlEqDWVccNnqihgJlpPWctoKe6iAZ9fro2uc2r3ptBlSgP6e9P7N4LZq469VUzeNYCILXp0EwX-fTExqn0dq-h4G46eYK6jqhjNBZEZf_oPu_BTyDDPFJKENJ02VqfpI6eBjDMbeFUOwOmRG3WZGHTKjTpnJ71783cndq9uQZODNEXCD9WEPNz70nUow9z7YAIN2McP__eM30l3SGA</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2391267164</pqid></control><display><type>article</type><title>Protective role of N-acetyl-l-tryptophan against hepatic ischemia-reperfusion injury via the RIP2/caspase-1/IL-1β signaling pathway</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Access via Taylor & Francis (Open Access Collection)</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><creator>Wang, Jianxin ; Yu, Shuna ; Li, Jianguo ; Li, Huiting ; Jiang, Hongxin ; Xiao, Peilun ; Pan, Yitong ; Zheng, Jie ; Yu, Li ; Jiang, Jiying</creator><creatorcontrib>Wang, Jianxin ; Yu, Shuna ; Li, Jianguo ; Li, Huiting ; Jiang, Hongxin ; Xiao, Peilun ; Pan, Yitong ; Zheng, Jie ; Yu, Li ; Jiang, Jiying</creatorcontrib><description>Context: Hepatic ischemia-reperfusion injury (HIRI) is a complex process observed during liver resection and transplantation. N-acetyl-l-tryptophan (l-NAT), an antagonist of neurokinin 1 receptor, has been used for the treatment of nausea and neurodegenerative diseases.
Objective: This study investigates the protective effect of l-NAT against HIRI and explores the potential underlying mechanisms.
Materials and methods: Adult male Sprague-Dawley (SD) rats were randomly divided into three groups: sham, I/R and I/R + l-NAT. HIRI model was generated by clamping the hepatic artery, portal vein and common bile duct with a microvascular bulldog clamp for 45 min, and then removing the clamp and allowing reperfusion for 6 h. BRL cells were exposed to 200 µM H
2
O
2
with or without 10 µM l-NAT for 6 h.
Results: After l-NAT intervention, the structure of hepatic lobules was intact, and no swelling was noted in the cells. Furthermore, cell viability was found to be significantly enhanced when compared with the controls (p < 0.05). The mRNA and protein expression levels of serine-threonine kinase 2 (RIP2) and interleukin-1β (IL-1β) were significantly increased in the I/R and H
2
O
2
groups when compared with the controls; however, these levels were significantly decreased after l-NAT intervention. Similarly, IL-1β activity and caspase-1 activity were significantly decreased in the H
2
O
2
group when compared with the controls, after l-NAT intervention.
Conclusions: Our findings indicated that l-NAT may exert a hepatoprotective role in HIRI through inhibiting RIP2/caspase-1/IL-1β signaling pathway, which can provide evidence for l-NAT to be a potential effective drug against HIRI during clinical practice.</description><identifier>ISSN: 1388-0209</identifier><identifier>ISSN: 1744-5116</identifier><identifier>EISSN: 1744-5116</identifier><identifier>DOI: 10.1080/13880209.2019.1617750</identifier><identifier>PMID: 31184936</identifier><language>eng</language><publisher>England: Taylor & Francis</publisher><subject>Animals ; Apoptosis - drug effects ; Bile ; Bile ducts ; Caspase 1 - metabolism ; Caspase-1 ; Cell Survival - drug effects ; Cell viability ; Gene expression ; Hepatic artery ; Hepatic ischemia-reperfusion injury ; Hydrogen peroxide ; Hydrogen Peroxide - metabolism ; IL-1β ; Interleukin-1beta - metabolism ; Ischemia ; Kinases ; Liver - blood supply ; Liver - drug effects ; Liver - metabolism ; Liver - pathology ; Male ; Microvasculature ; mRNA ; N-acetyl-l-tryptophan ; Nausea ; Neurodegenerative diseases ; Neurokinin ; Neurokinin NK1 receptors ; oxidative damaged ; Oxidative Stress - drug effects ; Portal vein ; Protein-serine/threonine kinase ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptor-Interacting Protein Serine-Threonine Kinase 2 - metabolism ; Reperfusion ; Reperfusion Injury - drug therapy ; Reperfusion Injury - metabolism ; Reperfusion Injury - prevention & control ; Reperfusion Injury - surgery ; Signal transduction ; Signal Transduction - drug effects ; Tryptophan ; Tryptophan - analogs & derivatives ; Tryptophan - pharmacology</subject><ispartof>Pharmaceutical biology, 2019-01, Vol.57 (1), p.385-391</ispartof><rights>2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. 2019</rights><rights>2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This work is licensed under the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. 2019 The Author(s)</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c562t-9e707470ad9c788c4d893202447bd24beb0590bdbf235c5f1993d132ddb9313f3</citedby><cites>FETCH-LOGICAL-c562t-9e707470ad9c788c4d893202447bd24beb0590bdbf235c5f1993d132ddb9313f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6566838/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6566838/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,27502,27924,27925,53791,53793,59143,59144</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31184936$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Jianxin</creatorcontrib><creatorcontrib>Yu, Shuna</creatorcontrib><creatorcontrib>Li, Jianguo</creatorcontrib><creatorcontrib>Li, Huiting</creatorcontrib><creatorcontrib>Jiang, Hongxin</creatorcontrib><creatorcontrib>Xiao, Peilun</creatorcontrib><creatorcontrib>Pan, Yitong</creatorcontrib><creatorcontrib>Zheng, Jie</creatorcontrib><creatorcontrib>Yu, Li</creatorcontrib><creatorcontrib>Jiang, Jiying</creatorcontrib><title>Protective role of N-acetyl-l-tryptophan against hepatic ischemia-reperfusion injury via the RIP2/caspase-1/IL-1β signaling pathway</title><title>Pharmaceutical biology</title><addtitle>Pharm Biol</addtitle><description>Context: Hepatic ischemia-reperfusion injury (HIRI) is a complex process observed during liver resection and transplantation. N-acetyl-l-tryptophan (l-NAT), an antagonist of neurokinin 1 receptor, has been used for the treatment of nausea and neurodegenerative diseases.
Objective: This study investigates the protective effect of l-NAT against HIRI and explores the potential underlying mechanisms.
Materials and methods: Adult male Sprague-Dawley (SD) rats were randomly divided into three groups: sham, I/R and I/R + l-NAT. HIRI model was generated by clamping the hepatic artery, portal vein and common bile duct with a microvascular bulldog clamp for 45 min, and then removing the clamp and allowing reperfusion for 6 h. BRL cells were exposed to 200 µM H
2
O
2
with or without 10 µM l-NAT for 6 h.
Results: After l-NAT intervention, the structure of hepatic lobules was intact, and no swelling was noted in the cells. Furthermore, cell viability was found to be significantly enhanced when compared with the controls (p < 0.05). The mRNA and protein expression levels of serine-threonine kinase 2 (RIP2) and interleukin-1β (IL-1β) were significantly increased in the I/R and H
2
O
2
groups when compared with the controls; however, these levels were significantly decreased after l-NAT intervention. Similarly, IL-1β activity and caspase-1 activity were significantly decreased in the H
2
O
2
group when compared with the controls, after l-NAT intervention.
Conclusions: Our findings indicated that l-NAT may exert a hepatoprotective role in HIRI through inhibiting RIP2/caspase-1/IL-1β signaling pathway, which can provide evidence for l-NAT to be a potential effective drug against HIRI during clinical practice.</description><subject>Animals</subject><subject>Apoptosis - drug effects</subject><subject>Bile</subject><subject>Bile ducts</subject><subject>Caspase 1 - metabolism</subject><subject>Caspase-1</subject><subject>Cell Survival - drug effects</subject><subject>Cell viability</subject><subject>Gene expression</subject><subject>Hepatic artery</subject><subject>Hepatic ischemia-reperfusion injury</subject><subject>Hydrogen peroxide</subject><subject>Hydrogen Peroxide - metabolism</subject><subject>IL-1β</subject><subject>Interleukin-1beta - metabolism</subject><subject>Ischemia</subject><subject>Kinases</subject><subject>Liver - blood supply</subject><subject>Liver - drug effects</subject><subject>Liver - metabolism</subject><subject>Liver - pathology</subject><subject>Male</subject><subject>Microvasculature</subject><subject>mRNA</subject><subject>N-acetyl-l-tryptophan</subject><subject>Nausea</subject><subject>Neurodegenerative diseases</subject><subject>Neurokinin</subject><subject>Neurokinin NK1 receptors</subject><subject>oxidative damaged</subject><subject>Oxidative Stress - drug effects</subject><subject>Portal vein</subject><subject>Protein-serine/threonine kinase</subject><subject>Random Allocation</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Receptor-Interacting Protein Serine-Threonine Kinase 2 - metabolism</subject><subject>Reperfusion</subject><subject>Reperfusion Injury - drug therapy</subject><subject>Reperfusion Injury - metabolism</subject><subject>Reperfusion Injury - prevention & control</subject><subject>Reperfusion Injury - surgery</subject><subject>Signal transduction</subject><subject>Signal Transduction - drug effects</subject><subject>Tryptophan</subject><subject>Tryptophan - analogs & derivatives</subject><subject>Tryptophan - pharmacology</subject><issn>1388-0209</issn><issn>1744-5116</issn><issn>1744-5116</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>0YH</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>DOA</sourceid><recordid>eNp9ksuO0zAUhiMEYoaBRwBZYsMmrS9JbG8QaMSlUgUjBGvrxLFbV2kcbGdG2fNEPAjPhEs7I4YFK1v258_nHP1F8ZzgBcECLwkTAlMsFxQTuSAN4bzGD4pzwquqrAlpHuZ9ZsoDdFY8iXGHMa4Zqx8XZ4wQUUnWnBc_roJPRid3bVDwvUHeok8laJPmvuzLFOYx-XELA4INuCEmtDUjJKeRi3pr9g7KYEYT7BSdH5AbdlOY0bUDlLYGfVld0aWGOEI0JVmu1iX59RNFtxmgd8MGZdP2BuanxSMLfTTPTutF8e39u6-XH8v15w-ry7frUtcNTaU0HPOKY-ik5kLoqhOSUUyrircdrVrT4lritmstZbWuLZGSdYTRrmslI8yyi2J19HYedmoMbg9hVh6c-nPgw0ZByL31RlEqDWVccNnqihgJlpPWctoKe6iAZ9fro2uc2r3ptBlSgP6e9P7N4LZq469VUzeNYCILXp0EwX-fTExqn0dq-h4G46eYK6jqhjNBZEZf_oPu_BTyDDPFJKENJ02VqfpI6eBjDMbeFUOwOmRG3WZGHTKjTpnJ71783cndq9uQZODNEXCD9WEPNz70nUow9z7YAIN2McP__eM30l3SGA</recordid><startdate>20190101</startdate><enddate>20190101</enddate><creator>Wang, Jianxin</creator><creator>Yu, Shuna</creator><creator>Li, Jianguo</creator><creator>Li, Huiting</creator><creator>Jiang, Hongxin</creator><creator>Xiao, Peilun</creator><creator>Pan, Yitong</creator><creator>Zheng, Jie</creator><creator>Yu, Li</creator><creator>Jiang, Jiying</creator><general>Taylor & Francis</general><general>Taylor & Francis Ltd</general><general>Taylor & Francis Group</general><scope>0YH</scope><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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20190101</creationdate><title>Protective role of N-acetyl-l-tryptophan against hepatic ischemia-reperfusion injury via the RIP2/caspase-1/IL-1β signaling pathway</title><author>Wang, Jianxin ; Yu, Shuna ; Li, Jianguo ; Li, Huiting ; Jiang, Hongxin ; Xiao, Peilun ; Pan, Yitong ; Zheng, Jie ; Yu, Li ; Jiang, Jiying</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c562t-9e707470ad9c788c4d893202447bd24beb0590bdbf235c5f1993d132ddb9313f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Animals</topic><topic>Apoptosis - drug effects</topic><topic>Bile</topic><topic>Bile ducts</topic><topic>Caspase 1 - metabolism</topic><topic>Caspase-1</topic><topic>Cell Survival - drug effects</topic><topic>Cell viability</topic><topic>Gene expression</topic><topic>Hepatic artery</topic><topic>Hepatic ischemia-reperfusion injury</topic><topic>Hydrogen peroxide</topic><topic>Hydrogen Peroxide - metabolism</topic><topic>IL-1β</topic><topic>Interleukin-1beta - metabolism</topic><topic>Ischemia</topic><topic>Kinases</topic><topic>Liver - blood supply</topic><topic>Liver - drug effects</topic><topic>Liver - metabolism</topic><topic>Liver - pathology</topic><topic>Male</topic><topic>Microvasculature</topic><topic>mRNA</topic><topic>N-acetyl-l-tryptophan</topic><topic>Nausea</topic><topic>Neurodegenerative diseases</topic><topic>Neurokinin</topic><topic>Neurokinin NK1 receptors</topic><topic>oxidative damaged</topic><topic>Oxidative Stress - drug effects</topic><topic>Portal vein</topic><topic>Protein-serine/threonine kinase</topic><topic>Random Allocation</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Receptor-Interacting Protein Serine-Threonine Kinase 2 - metabolism</topic><topic>Reperfusion</topic><topic>Reperfusion Injury - drug therapy</topic><topic>Reperfusion Injury - metabolism</topic><topic>Reperfusion Injury - prevention & control</topic><topic>Reperfusion Injury - surgery</topic><topic>Signal transduction</topic><topic>Signal Transduction - drug effects</topic><topic>Tryptophan</topic><topic>Tryptophan - analogs & derivatives</topic><topic>Tryptophan - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Jianxin</creatorcontrib><creatorcontrib>Yu, Shuna</creatorcontrib><creatorcontrib>Li, Jianguo</creatorcontrib><creatorcontrib>Li, Huiting</creatorcontrib><creatorcontrib>Jiang, Hongxin</creatorcontrib><creatorcontrib>Xiao, Peilun</creatorcontrib><creatorcontrib>Pan, Yitong</creatorcontrib><creatorcontrib>Zheng, Jie</creatorcontrib><creatorcontrib>Yu, Li</creatorcontrib><creatorcontrib>Jiang, Jiying</creatorcontrib><collection>Access via Taylor & Francis (Open Access Collection)</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Technology Research Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Pharmaceutical biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Jianxin</au><au>Yu, Shuna</au><au>Li, Jianguo</au><au>Li, Huiting</au><au>Jiang, Hongxin</au><au>Xiao, Peilun</au><au>Pan, Yitong</au><au>Zheng, Jie</au><au>Yu, Li</au><au>Jiang, Jiying</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Protective role of N-acetyl-l-tryptophan against hepatic ischemia-reperfusion injury via the RIP2/caspase-1/IL-1β signaling pathway</atitle><jtitle>Pharmaceutical biology</jtitle><addtitle>Pharm Biol</addtitle><date>2019-01-01</date><risdate>2019</risdate><volume>57</volume><issue>1</issue><spage>385</spage><epage>391</epage><pages>385-391</pages><issn>1388-0209</issn><issn>1744-5116</issn><eissn>1744-5116</eissn><abstract>Context: Hepatic ischemia-reperfusion injury (HIRI) is a complex process observed during liver resection and transplantation. N-acetyl-l-tryptophan (l-NAT), an antagonist of neurokinin 1 receptor, has been used for the treatment of nausea and neurodegenerative diseases.
Objective: This study investigates the protective effect of l-NAT against HIRI and explores the potential underlying mechanisms.
Materials and methods: Adult male Sprague-Dawley (SD) rats were randomly divided into three groups: sham, I/R and I/R + l-NAT. HIRI model was generated by clamping the hepatic artery, portal vein and common bile duct with a microvascular bulldog clamp for 45 min, and then removing the clamp and allowing reperfusion for 6 h. BRL cells were exposed to 200 µM H
2
O
2
with or without 10 µM l-NAT for 6 h.
Results: After l-NAT intervention, the structure of hepatic lobules was intact, and no swelling was noted in the cells. Furthermore, cell viability was found to be significantly enhanced when compared with the controls (p < 0.05). The mRNA and protein expression levels of serine-threonine kinase 2 (RIP2) and interleukin-1β (IL-1β) were significantly increased in the I/R and H
2
O
2
groups when compared with the controls; however, these levels were significantly decreased after l-NAT intervention. Similarly, IL-1β activity and caspase-1 activity were significantly decreased in the H
2
O
2
group when compared with the controls, after l-NAT intervention.
Conclusions: Our findings indicated that l-NAT may exert a hepatoprotective role in HIRI through inhibiting RIP2/caspase-1/IL-1β signaling pathway, which can provide evidence for l-NAT to be a potential effective drug against HIRI during clinical practice.</abstract><cop>England</cop><pub>Taylor & Francis</pub><pmid>31184936</pmid><doi>10.1080/13880209.2019.1617750</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Pharmaceutical biology, 2019-01, Vol.57 (1), p.385-391 |
| issn | 1388-0209 1744-5116 1744-5116 |
| language | eng |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Access via Taylor & Francis (Open Access Collection); PubMed Central; Alma/SFX Local Collection |
| subjects | Animals Apoptosis - drug effects Bile Bile ducts Caspase 1 - metabolism Caspase-1 Cell Survival - drug effects Cell viability Gene expression Hepatic artery Hepatic ischemia-reperfusion injury Hydrogen peroxide Hydrogen Peroxide - metabolism IL-1β Interleukin-1beta - metabolism Ischemia Kinases Liver - blood supply Liver - drug effects Liver - metabolism Liver - pathology Male Microvasculature mRNA N-acetyl-l-tryptophan Nausea Neurodegenerative diseases Neurokinin Neurokinin NK1 receptors oxidative damaged Oxidative Stress - drug effects Portal vein Protein-serine/threonine kinase Random Allocation Rats Rats, Sprague-Dawley Receptor-Interacting Protein Serine-Threonine Kinase 2 - metabolism Reperfusion Reperfusion Injury - drug therapy Reperfusion Injury - metabolism Reperfusion Injury - prevention & control Reperfusion Injury - surgery Signal transduction Signal Transduction - drug effects Tryptophan Tryptophan - analogs & derivatives Tryptophan - pharmacology |
| title | Protective role of N-acetyl-l-tryptophan against hepatic ischemia-reperfusion injury via the RIP2/caspase-1/IL-1β signaling pathway |
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