Amelioration of hepatic ischemia/reperfusion injury in the remnant liver after partial hepatectomy in rats
Background and Aims: Reactive oxygen species have been implicated in the development of hepatic ischemia/reperfusion (I/R) injury. I/R injury remains an important problem in massive hepatectomy and organ transplantation. The aim of this study was to examine the effect of edaravone, a newly synthesi...
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| Veröffentlicht in: | Journal of gastroenterology and hepatology 2007-12, Vol.22 (12), p.2167-2172 |
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| creator | Hiranuma, Susumu Ito, Koji Noda, Yumi Ozasa, Hisashi Koike, Yuichi Horikawa, Saburo |
| description | Background and Aims: Reactive oxygen species have been implicated in the development of hepatic ischemia/reperfusion (I/R) injury. I/R injury remains an important problem in massive hepatectomy and organ transplantation. The aim of this study was to examine the effect of edaravone, a newly synthesized free radical scavenger, on I/R injury in the remnant liver after partial hepatectomy in rats.
Methods: Partial (70%) hepatic ischemia was induced in rats by occluding the hepatic artery, portal vein, and bile duct to left and median lobes of liver. Total hepatic ischemia (Pringle maneuver) was induced by occluding the hepatoduodenal ligament. Edaravone was intravenously administered to rats just before reperfusion and partial (70%) hepatectomy was performed just after reperfusion.
Results: Edaravone significantly reduced the increases in the levels of serum alanine aminotransferase and aspartate aminotransferase in rats with liver injury induced by 90‐min of partial ischemia followed by 120‐min of reperfusion. Histopathological analysis showed that edaravone prevented inflammatory changes in the livers with I/R injury. Edaravone also decreased the levels of myeloperoxidase activity, which is an index of neutrophil infiltration, and interleukin‐6 mRNA, which is a proinflammatory cytokine. Additionally, edaravone improved the survival rate in partial hepatectomy rats with I/R injury induced by the Pringle maneuver.
Conclusions: Edaravone administration prior to reperfusion protected the liver against I/R injury. Edaravone also improved the function of the remnant liver with I/R injury after partial hepatectomy. Therefore, edaravone may have applicability for major hepatectomy and liver transplantation in the clinical setting. |
| doi_str_mv | 10.1111/j.1440-1746.2006.04779.x |
| format | Article |
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Methods: Partial (70%) hepatic ischemia was induced in rats by occluding the hepatic artery, portal vein, and bile duct to left and median lobes of liver. Total hepatic ischemia (Pringle maneuver) was induced by occluding the hepatoduodenal ligament. Edaravone was intravenously administered to rats just before reperfusion and partial (70%) hepatectomy was performed just after reperfusion.
Results: Edaravone significantly reduced the increases in the levels of serum alanine aminotransferase and aspartate aminotransferase in rats with liver injury induced by 90‐min of partial ischemia followed by 120‐min of reperfusion. Histopathological analysis showed that edaravone prevented inflammatory changes in the livers with I/R injury. Edaravone also decreased the levels of myeloperoxidase activity, which is an index of neutrophil infiltration, and interleukin‐6 mRNA, which is a proinflammatory cytokine. Additionally, edaravone improved the survival rate in partial hepatectomy rats with I/R injury induced by the Pringle maneuver.
Conclusions: Edaravone administration prior to reperfusion protected the liver against I/R injury. Edaravone also improved the function of the remnant liver with I/R injury after partial hepatectomy. Therefore, edaravone may have applicability for major hepatectomy and liver transplantation in the clinical setting.</description><identifier>ISSN: 0815-9319</identifier><identifier>EISSN: 1440-1746</identifier><identifier>DOI: 10.1111/j.1440-1746.2006.04779.x</identifier><identifier>PMID: 18031376</identifier><language>eng</language><publisher>Melbourne, Australia: Blackwell Publishing Asia</publisher><subject>Animals ; Antipyrine - analogs & derivatives ; Antipyrine - pharmacology ; Biological and medical sciences ; Cardiology. Vascular system ; Free Radical Scavengers - pharmacology ; Gastroenterology. Liver. Pancreas. Abdomen ; Gene Expression Regulation - drug effects ; Hepatectomy - methods ; Interleukin-6 - genetics ; Interleukin-6 - metabolism ; ischemia/reperfusion ; liver ; Liver - drug effects ; Liver - enzymology ; Liver - metabolism ; Liver - pathology ; Liver Diseases - enzymology ; Liver Diseases - mortality ; Liver Diseases - pathology ; Liver, biliary tract, pancreas, portal circulation, spleen ; Liver. Biliary tract. Portal circulation. Exocrine pancreas ; Male ; Medical sciences ; neutrophil ; Other diseases. Semiology ; partial hepatectomy ; Peroxidase - metabolism ; Rats ; Rats, Wistar ; Reperfusion Injury - prevention & control ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases ; Surgery of the digestive system ; Survival Rate ; transplantation</subject><ispartof>Journal of gastroenterology and hepatology, 2007-12, Vol.22 (12), p.2167-2172</ispartof><rights>2008 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5019-d97181b8b8100463cca019484de46e9fe753480f5c83a7023b7d50a35389cdf43</citedby><cites>FETCH-LOGICAL-c5019-d97181b8b8100463cca019484de46e9fe753480f5c83a7023b7d50a35389cdf43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1440-1746.2006.04779.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1440-1746.2006.04779.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=19912613$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18031376$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hiranuma, Susumu</creatorcontrib><creatorcontrib>Ito, Koji</creatorcontrib><creatorcontrib>Noda, Yumi</creatorcontrib><creatorcontrib>Ozasa, Hisashi</creatorcontrib><creatorcontrib>Koike, Yuichi</creatorcontrib><creatorcontrib>Horikawa, Saburo</creatorcontrib><title>Amelioration of hepatic ischemia/reperfusion injury in the remnant liver after partial hepatectomy in rats</title><title>Journal of gastroenterology and hepatology</title><addtitle>J Gastroenterol Hepatol</addtitle><description>Background and Aims: Reactive oxygen species have been implicated in the development of hepatic ischemia/reperfusion (I/R) injury. I/R injury remains an important problem in massive hepatectomy and organ transplantation. The aim of this study was to examine the effect of edaravone, a newly synthesized free radical scavenger, on I/R injury in the remnant liver after partial hepatectomy in rats.
Methods: Partial (70%) hepatic ischemia was induced in rats by occluding the hepatic artery, portal vein, and bile duct to left and median lobes of liver. Total hepatic ischemia (Pringle maneuver) was induced by occluding the hepatoduodenal ligament. Edaravone was intravenously administered to rats just before reperfusion and partial (70%) hepatectomy was performed just after reperfusion.
Results: Edaravone significantly reduced the increases in the levels of serum alanine aminotransferase and aspartate aminotransferase in rats with liver injury induced by 90‐min of partial ischemia followed by 120‐min of reperfusion. Histopathological analysis showed that edaravone prevented inflammatory changes in the livers with I/R injury. Edaravone also decreased the levels of myeloperoxidase activity, which is an index of neutrophil infiltration, and interleukin‐6 mRNA, which is a proinflammatory cytokine. Additionally, edaravone improved the survival rate in partial hepatectomy rats with I/R injury induced by the Pringle maneuver.
Conclusions: Edaravone administration prior to reperfusion protected the liver against I/R injury. Edaravone also improved the function of the remnant liver with I/R injury after partial hepatectomy. Therefore, edaravone may have applicability for major hepatectomy and liver transplantation in the clinical setting.</description><subject>Animals</subject><subject>Antipyrine - analogs & derivatives</subject><subject>Antipyrine - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Cardiology. Vascular system</subject><subject>Free Radical Scavengers - pharmacology</subject><subject>Gastroenterology. Liver. Pancreas. Abdomen</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Hepatectomy - methods</subject><subject>Interleukin-6 - genetics</subject><subject>Interleukin-6 - metabolism</subject><subject>ischemia/reperfusion</subject><subject>liver</subject><subject>Liver - drug effects</subject><subject>Liver - enzymology</subject><subject>Liver - metabolism</subject><subject>Liver - pathology</subject><subject>Liver Diseases - enzymology</subject><subject>Liver Diseases - mortality</subject><subject>Liver Diseases - pathology</subject><subject>Liver, biliary tract, pancreas, portal circulation, spleen</subject><subject>Liver. Biliary tract. Portal circulation. Exocrine pancreas</subject><subject>Male</subject><subject>Medical sciences</subject><subject>neutrophil</subject><subject>Other diseases. Semiology</subject><subject>partial hepatectomy</subject><subject>Peroxidase - metabolism</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Reperfusion Injury - prevention & control</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</subject><subject>Surgery of the digestive system</subject><subject>Survival Rate</subject><subject>transplantation</subject><issn>0815-9319</issn><issn>1440-1746</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkE1v3CAQhlHVKtmm-QuVL-3NDixg4NBDFDWbRqv20FQ5IhYPWlx_Fexm998Xx6vkWg7MiHnemeFFKCO4IOlc1QVhDOdEsLJYY1wWmAmhisMbtHopvEUrLAnPFSXqHL2PscYYMyz4GTonElNCRblC9XULje-DGX3fZb3L9jCk3GY-2j203lwFGCC4Kc5139VTOKaQjXvIArSd6cas8X8hZMaN6R5MGL1pljZgx759xlP_-AG9c6aJcHmKF-jX7deHm7t8-2Pz7eZ6m1uOicorJYgkO7mTJO1bUmtNemaSVcBKUA4Ep0xix62kRuA13YmKY0M5lcpWjtEL9HnpO4T-zwRx1G36DDSN6aCfoi4lZ4yWNIFyAW3oYwzg9BB8a8JRE6xnn3WtZzv1bKeefdbPPutDkn48zZh2LVSvwpOxCfh0Aky0pnHBdNbHV04psi7JvMOXhXvyDRz_ewF9v7mbs6TPF72PIxxe9Cb81qWgguvH7xt9T38-PGIu9Zb-AwoxqMY</recordid><startdate>200712</startdate><enddate>200712</enddate><creator>Hiranuma, Susumu</creator><creator>Ito, Koji</creator><creator>Noda, Yumi</creator><creator>Ozasa, Hisashi</creator><creator>Koike, Yuichi</creator><creator>Horikawa, Saburo</creator><general>Blackwell Publishing Asia</general><general>Blackwell Science</general><scope>BSCLL</scope><scope>IQODW</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>7X8</scope></search><sort><creationdate>200712</creationdate><title>Amelioration of hepatic ischemia/reperfusion injury in the remnant liver after partial hepatectomy in rats</title><author>Hiranuma, Susumu ; Ito, Koji ; Noda, Yumi ; Ozasa, Hisashi ; Koike, Yuichi ; Horikawa, Saburo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5019-d97181b8b8100463cca019484de46e9fe753480f5c83a7023b7d50a35389cdf43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Animals</topic><topic>Antipyrine - analogs & derivatives</topic><topic>Antipyrine - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Cardiology. Vascular system</topic><topic>Free Radical Scavengers - pharmacology</topic><topic>Gastroenterology. Liver. Pancreas. Abdomen</topic><topic>Gene Expression Regulation - drug effects</topic><topic>Hepatectomy - methods</topic><topic>Interleukin-6 - genetics</topic><topic>Interleukin-6 - metabolism</topic><topic>ischemia/reperfusion</topic><topic>liver</topic><topic>Liver - drug effects</topic><topic>Liver - enzymology</topic><topic>Liver - metabolism</topic><topic>Liver - pathology</topic><topic>Liver Diseases - enzymology</topic><topic>Liver Diseases - mortality</topic><topic>Liver Diseases - pathology</topic><topic>Liver, biliary tract, pancreas, portal circulation, spleen</topic><topic>Liver. Biliary tract. Portal circulation. Exocrine pancreas</topic><topic>Male</topic><topic>Medical sciences</topic><topic>neutrophil</topic><topic>Other diseases. Semiology</topic><topic>partial hepatectomy</topic><topic>Peroxidase - metabolism</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Reperfusion Injury - prevention & control</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</topic><topic>Surgery of the digestive system</topic><topic>Survival Rate</topic><topic>transplantation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hiranuma, Susumu</creatorcontrib><creatorcontrib>Ito, Koji</creatorcontrib><creatorcontrib>Noda, Yumi</creatorcontrib><creatorcontrib>Ozasa, Hisashi</creatorcontrib><creatorcontrib>Koike, Yuichi</creatorcontrib><creatorcontrib>Horikawa, Saburo</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><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>Journal of gastroenterology and hepatology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hiranuma, Susumu</au><au>Ito, Koji</au><au>Noda, Yumi</au><au>Ozasa, Hisashi</au><au>Koike, Yuichi</au><au>Horikawa, Saburo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Amelioration of hepatic ischemia/reperfusion injury in the remnant liver after partial hepatectomy in rats</atitle><jtitle>Journal of gastroenterology and hepatology</jtitle><addtitle>J Gastroenterol Hepatol</addtitle><date>2007-12</date><risdate>2007</risdate><volume>22</volume><issue>12</issue><spage>2167</spage><epage>2172</epage><pages>2167-2172</pages><issn>0815-9319</issn><eissn>1440-1746</eissn><abstract>Background and Aims: Reactive oxygen species have been implicated in the development of hepatic ischemia/reperfusion (I/R) injury. I/R injury remains an important problem in massive hepatectomy and organ transplantation. The aim of this study was to examine the effect of edaravone, a newly synthesized free radical scavenger, on I/R injury in the remnant liver after partial hepatectomy in rats.
Methods: Partial (70%) hepatic ischemia was induced in rats by occluding the hepatic artery, portal vein, and bile duct to left and median lobes of liver. Total hepatic ischemia (Pringle maneuver) was induced by occluding the hepatoduodenal ligament. Edaravone was intravenously administered to rats just before reperfusion and partial (70%) hepatectomy was performed just after reperfusion.
Results: Edaravone significantly reduced the increases in the levels of serum alanine aminotransferase and aspartate aminotransferase in rats with liver injury induced by 90‐min of partial ischemia followed by 120‐min of reperfusion. Histopathological analysis showed that edaravone prevented inflammatory changes in the livers with I/R injury. Edaravone also decreased the levels of myeloperoxidase activity, which is an index of neutrophil infiltration, and interleukin‐6 mRNA, which is a proinflammatory cytokine. Additionally, edaravone improved the survival rate in partial hepatectomy rats with I/R injury induced by the Pringle maneuver.
Conclusions: Edaravone administration prior to reperfusion protected the liver against I/R injury. Edaravone also improved the function of the remnant liver with I/R injury after partial hepatectomy. Therefore, edaravone may have applicability for major hepatectomy and liver transplantation in the clinical setting.</abstract><cop>Melbourne, Australia</cop><pub>Blackwell Publishing Asia</pub><pmid>18031376</pmid><doi>10.1111/j.1440-1746.2006.04779.x</doi><tpages>6</tpages></addata></record> |
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| subjects | Animals Antipyrine - analogs & derivatives Antipyrine - pharmacology Biological and medical sciences Cardiology. Vascular system Free Radical Scavengers - pharmacology Gastroenterology. Liver. Pancreas. Abdomen Gene Expression Regulation - drug effects Hepatectomy - methods Interleukin-6 - genetics Interleukin-6 - metabolism ischemia/reperfusion liver Liver - drug effects Liver - enzymology Liver - metabolism Liver - pathology Liver Diseases - enzymology Liver Diseases - mortality Liver Diseases - pathology Liver, biliary tract, pancreas, portal circulation, spleen Liver. Biliary tract. Portal circulation. Exocrine pancreas Male Medical sciences neutrophil Other diseases. Semiology partial hepatectomy Peroxidase - metabolism Rats Rats, Wistar Reperfusion Injury - prevention & control RNA, Messenger - genetics RNA, Messenger - metabolism Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases Surgery of the digestive system Survival Rate transplantation |
| title | Amelioration of hepatic ischemia/reperfusion injury in the remnant liver after partial hepatectomy in rats |
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