A novel inhibitor of inducible nitric oxide synthase (ONO-1714) prevents critical warm ischemia-reperfusion injury in the pig liver
Recently, a novel inhibitor of inducible nitric oxide synthase, ONO-1714, was developed. We evaluated the effect of ONO-1714 on a critical warm I/R model of the pig liver. Pigs were subjected to 180 min of hepatic warm I/R under the extracorporeal circulation. We investigated the time course of chan...
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| Veröffentlicht in: | Transplantation 2002-05, Vol.73 (9), p.1439-1446 |
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| creator | MEGURO, Makoto KATSURAMAKI, Tadashi NAGAYAMA, Minoru KIMURA, Hitoshi ISOBE, Masato KIMURA, Yasutoshi MATSUNO, Takashi NUI, Akihiro HIRATA, Koichi |
| description | Recently, a novel inhibitor of inducible nitric oxide synthase, ONO-1714, was developed. We evaluated the effect of ONO-1714 on a critical warm I/R model of the pig liver.
Pigs were subjected to 180 min of hepatic warm I/R under the extracorporeal circulation. We investigated the time course of changes in the serum NO2- + NO3- (NOx), the cellular distribution of endothelial and inducible nitric oxide synthase, thrombocyte-thrombi, and nitrotyrosine by immunohistochemistry. The hepatic tissue blood flow (HTBF) was measured continuously using a laser-Doppler blood flowmeter.
ONO-1714 at 0.05 mg/kg improved the survival rate from 54 (control group) to 100%. The serum NOx levels in the ONO-1714 group were significantly lower than those in the control group at 1, 1.5, 2, 3, and 6 hr after reperfusion. The serum aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) levels of the ONO-1714 group were significantly lower than the control group, and the HTBF of the ONO-1714 group was significantly higher than the control group. The formation of thrombocyte-thrombi and nitrotyrosine after reperfusion was significantly lower in the ONO-1714 group.
These results indicated that ONO-1714 improved the survival rates and attenuated I/R injury in a critical hepatic warm I/R model of the pig. ONO-1714 will be beneficial for hepatectomy or liver transplantation in the clinical field. |
| doi_str_mv | 10.1097/00007890-200205150-00013 |
| format | Article |
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Pigs were subjected to 180 min of hepatic warm I/R under the extracorporeal circulation. We investigated the time course of changes in the serum NO2- + NO3- (NOx), the cellular distribution of endothelial and inducible nitric oxide synthase, thrombocyte-thrombi, and nitrotyrosine by immunohistochemistry. The hepatic tissue blood flow (HTBF) was measured continuously using a laser-Doppler blood flowmeter.
ONO-1714 at 0.05 mg/kg improved the survival rate from 54 (control group) to 100%. The serum NOx levels in the ONO-1714 group were significantly lower than those in the control group at 1, 1.5, 2, 3, and 6 hr after reperfusion. The serum aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) levels of the ONO-1714 group were significantly lower than the control group, and the HTBF of the ONO-1714 group was significantly higher than the control group. The formation of thrombocyte-thrombi and nitrotyrosine after reperfusion was significantly lower in the ONO-1714 group.
These results indicated that ONO-1714 improved the survival rates and attenuated I/R injury in a critical hepatic warm I/R model of the pig. ONO-1714 will be beneficial for hepatectomy or liver transplantation in the clinical field.</description><identifier>ISSN: 0041-1337</identifier><identifier>DOI: 10.1097/00007890-200205150-00013</identifier><identifier>PMID: 12023622</identifier><identifier>CODEN: TRPLAU</identifier><language>eng</language><publisher>Hagerstown, MD: Lippincott</publisher><subject>Amidines - pharmacology ; Animals ; Aspartate Aminotransferases - blood ; Biological and medical sciences ; Enzyme Inhibitors - pharmacology ; Female ; Heterocyclic Compounds, 2-Ring - pharmacology ; Hot Temperature ; Ischemia - pathology ; Ischemia - physiopathology ; L-Lactate Dehydrogenase - blood ; Liver - drug effects ; Liver - metabolism ; Liver - pathology ; Liver Circulation - drug effects ; Liver, biliary tract, pancreas, portal circulation, spleen ; Medical sciences ; Nitrates - blood ; Nitric Oxide Synthase - antagonists & inhibitors ; Nitric Oxide Synthase - metabolism ; Nitric Oxide Synthase Type II ; Nitric Oxide Synthase Type III ; Nitrites - blood ; Reperfusion Injury - pathology ; Reperfusion Injury - physiopathology ; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases ; Surgery of the digestive system ; Survival Analysis ; Swine ; Thrombosis - prevention & control ; Tissue Distribution ; Tyrosine - analogs & derivatives ; Tyrosine - metabolism</subject><ispartof>Transplantation, 2002-05, Vol.73 (9), p.1439-1446</ispartof><rights>2002 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c488t-ca707d385d20038bc37e2867152c674f6b3f7a5fd7eacb6d792124cd04495aa23</citedby><cites>FETCH-LOGICAL-c488t-ca707d385d20038bc37e2867152c674f6b3f7a5fd7eacb6d792124cd04495aa23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,778,782,27911,27912</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=13671779$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12023622$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>MEGURO, Makoto</creatorcontrib><creatorcontrib>KATSURAMAKI, Tadashi</creatorcontrib><creatorcontrib>NAGAYAMA, Minoru</creatorcontrib><creatorcontrib>KIMURA, Hitoshi</creatorcontrib><creatorcontrib>ISOBE, Masato</creatorcontrib><creatorcontrib>KIMURA, Yasutoshi</creatorcontrib><creatorcontrib>MATSUNO, Takashi</creatorcontrib><creatorcontrib>NUI, Akihiro</creatorcontrib><creatorcontrib>HIRATA, Koichi</creatorcontrib><title>A novel inhibitor of inducible nitric oxide synthase (ONO-1714) prevents critical warm ischemia-reperfusion injury in the pig liver</title><title>Transplantation</title><addtitle>Transplantation</addtitle><description>Recently, a novel inhibitor of inducible nitric oxide synthase, ONO-1714, was developed. We evaluated the effect of ONO-1714 on a critical warm I/R model of the pig liver.
Pigs were subjected to 180 min of hepatic warm I/R under the extracorporeal circulation. We investigated the time course of changes in the serum NO2- + NO3- (NOx), the cellular distribution of endothelial and inducible nitric oxide synthase, thrombocyte-thrombi, and nitrotyrosine by immunohistochemistry. The hepatic tissue blood flow (HTBF) was measured continuously using a laser-Doppler blood flowmeter.
ONO-1714 at 0.05 mg/kg improved the survival rate from 54 (control group) to 100%. The serum NOx levels in the ONO-1714 group were significantly lower than those in the control group at 1, 1.5, 2, 3, and 6 hr after reperfusion. The serum aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) levels of the ONO-1714 group were significantly lower than the control group, and the HTBF of the ONO-1714 group was significantly higher than the control group. The formation of thrombocyte-thrombi and nitrotyrosine after reperfusion was significantly lower in the ONO-1714 group.
These results indicated that ONO-1714 improved the survival rates and attenuated I/R injury in a critical hepatic warm I/R model of the pig. ONO-1714 will be beneficial for hepatectomy or liver transplantation in the clinical field.</description><subject>Amidines - pharmacology</subject><subject>Animals</subject><subject>Aspartate Aminotransferases - blood</subject><subject>Biological and medical sciences</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Female</subject><subject>Heterocyclic Compounds, 2-Ring - pharmacology</subject><subject>Hot Temperature</subject><subject>Ischemia - pathology</subject><subject>Ischemia - physiopathology</subject><subject>L-Lactate Dehydrogenase - blood</subject><subject>Liver - drug effects</subject><subject>Liver - metabolism</subject><subject>Liver - pathology</subject><subject>Liver Circulation - drug effects</subject><subject>Liver, biliary tract, pancreas, portal circulation, spleen</subject><subject>Medical sciences</subject><subject>Nitrates - blood</subject><subject>Nitric Oxide Synthase - antagonists & inhibitors</subject><subject>Nitric Oxide Synthase - metabolism</subject><subject>Nitric Oxide Synthase Type II</subject><subject>Nitric Oxide Synthase Type III</subject><subject>Nitrites - blood</subject><subject>Reperfusion Injury - pathology</subject><subject>Reperfusion Injury - physiopathology</subject><subject>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</subject><subject>Surgery of the digestive system</subject><subject>Survival Analysis</subject><subject>Swine</subject><subject>Thrombosis - prevention & control</subject><subject>Tissue Distribution</subject><subject>Tyrosine - analogs & derivatives</subject><subject>Tyrosine - metabolism</subject><issn>0041-1337</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1PwzAMhnMAsTH4CygXEBwK-Wjr9jhNfEkTu8C5SlOXZeoXSTvYmT9OYIMd8cWy9dqJ34cQytk1ZyncMB-QpCwQjAkW8YgFvsPlARkzFvKASwkjcuzcyrcjCXBERlwwIWMhxuRzSpt2jRU1zdLkpm8tbUtfFIM2eYW0Mb01mrYfpkDqNk2_VA7p5eJpEXDg4RXtLK6x6R3V1vRGq4q-K1tT4_QSa6MCix3acnCmbfza1WA3PtF-ibQzr7Qya7Qn5LBUlcPTXZ6Ql7vb59lDMF_cP86m80CHSdIHWgGDQiZR4S-VSa4loEhi4JHQMYRlnMsSVFQWgErncQGp4CLUBQvDNFJKyAm52O7tbPs2oOuz2n8Tq0o12A4uAw7eHxb_K-RJKCHyHk9IshVq2zpnscw6a2plNxln2Ted7JdO9kcn-6HjR892bwx5jcV-cIfGC853AuW8raVVjTZur5P-coBUfgHnSJm-</recordid><startdate>20020515</startdate><enddate>20020515</enddate><creator>MEGURO, Makoto</creator><creator>KATSURAMAKI, Tadashi</creator><creator>NAGAYAMA, Minoru</creator><creator>KIMURA, Hitoshi</creator><creator>ISOBE, Masato</creator><creator>KIMURA, Yasutoshi</creator><creator>MATSUNO, Takashi</creator><creator>NUI, Akihiro</creator><creator>HIRATA, Koichi</creator><general>Lippincott</general><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>7T5</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20020515</creationdate><title>A novel inhibitor of inducible nitric oxide synthase (ONO-1714) prevents critical warm ischemia-reperfusion injury in the pig liver</title><author>MEGURO, Makoto ; KATSURAMAKI, Tadashi ; NAGAYAMA, Minoru ; KIMURA, Hitoshi ; ISOBE, Masato ; KIMURA, Yasutoshi ; MATSUNO, Takashi ; NUI, Akihiro ; HIRATA, Koichi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c488t-ca707d385d20038bc37e2867152c674f6b3f7a5fd7eacb6d792124cd04495aa23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Amidines - pharmacology</topic><topic>Animals</topic><topic>Aspartate Aminotransferases - blood</topic><topic>Biological and medical sciences</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Female</topic><topic>Heterocyclic Compounds, 2-Ring - pharmacology</topic><topic>Hot Temperature</topic><topic>Ischemia - pathology</topic><topic>Ischemia - physiopathology</topic><topic>L-Lactate Dehydrogenase - blood</topic><topic>Liver - drug effects</topic><topic>Liver - metabolism</topic><topic>Liver - pathology</topic><topic>Liver Circulation - drug effects</topic><topic>Liver, biliary tract, pancreas, portal circulation, spleen</topic><topic>Medical sciences</topic><topic>Nitrates - blood</topic><topic>Nitric Oxide Synthase - antagonists & inhibitors</topic><topic>Nitric Oxide Synthase - metabolism</topic><topic>Nitric Oxide Synthase Type II</topic><topic>Nitric Oxide Synthase Type III</topic><topic>Nitrites - blood</topic><topic>Reperfusion Injury - pathology</topic><topic>Reperfusion Injury - physiopathology</topic><topic>Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases</topic><topic>Surgery of the digestive system</topic><topic>Survival Analysis</topic><topic>Swine</topic><topic>Thrombosis - prevention & control</topic><topic>Tissue Distribution</topic><topic>Tyrosine - analogs & derivatives</topic><topic>Tyrosine - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>MEGURO, Makoto</creatorcontrib><creatorcontrib>KATSURAMAKI, Tadashi</creatorcontrib><creatorcontrib>NAGAYAMA, Minoru</creatorcontrib><creatorcontrib>KIMURA, Hitoshi</creatorcontrib><creatorcontrib>ISOBE, Masato</creatorcontrib><creatorcontrib>KIMURA, Yasutoshi</creatorcontrib><creatorcontrib>MATSUNO, Takashi</creatorcontrib><creatorcontrib>NUI, Akihiro</creatorcontrib><creatorcontrib>HIRATA, Koichi</creatorcontrib><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>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Transplantation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>MEGURO, Makoto</au><au>KATSURAMAKI, Tadashi</au><au>NAGAYAMA, Minoru</au><au>KIMURA, Hitoshi</au><au>ISOBE, Masato</au><au>KIMURA, Yasutoshi</au><au>MATSUNO, Takashi</au><au>NUI, Akihiro</au><au>HIRATA, Koichi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A novel inhibitor of inducible nitric oxide synthase (ONO-1714) prevents critical warm ischemia-reperfusion injury in the pig liver</atitle><jtitle>Transplantation</jtitle><addtitle>Transplantation</addtitle><date>2002-05-15</date><risdate>2002</risdate><volume>73</volume><issue>9</issue><spage>1439</spage><epage>1446</epage><pages>1439-1446</pages><issn>0041-1337</issn><coden>TRPLAU</coden><abstract>Recently, a novel inhibitor of inducible nitric oxide synthase, ONO-1714, was developed. We evaluated the effect of ONO-1714 on a critical warm I/R model of the pig liver.
Pigs were subjected to 180 min of hepatic warm I/R under the extracorporeal circulation. We investigated the time course of changes in the serum NO2- + NO3- (NOx), the cellular distribution of endothelial and inducible nitric oxide synthase, thrombocyte-thrombi, and nitrotyrosine by immunohistochemistry. The hepatic tissue blood flow (HTBF) was measured continuously using a laser-Doppler blood flowmeter.
ONO-1714 at 0.05 mg/kg improved the survival rate from 54 (control group) to 100%. The serum NOx levels in the ONO-1714 group were significantly lower than those in the control group at 1, 1.5, 2, 3, and 6 hr after reperfusion. The serum aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) levels of the ONO-1714 group were significantly lower than the control group, and the HTBF of the ONO-1714 group was significantly higher than the control group. The formation of thrombocyte-thrombi and nitrotyrosine after reperfusion was significantly lower in the ONO-1714 group.
These results indicated that ONO-1714 improved the survival rates and attenuated I/R injury in a critical hepatic warm I/R model of the pig. ONO-1714 will be beneficial for hepatectomy or liver transplantation in the clinical field.</abstract><cop>Hagerstown, MD</cop><pub>Lippincott</pub><pmid>12023622</pmid><doi>10.1097/00007890-200205150-00013</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Transplantation, 2002-05, Vol.73 (9), p.1439-1446 |
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| subjects | Amidines - pharmacology Animals Aspartate Aminotransferases - blood Biological and medical sciences Enzyme Inhibitors - pharmacology Female Heterocyclic Compounds, 2-Ring - pharmacology Hot Temperature Ischemia - pathology Ischemia - physiopathology L-Lactate Dehydrogenase - blood Liver - drug effects Liver - metabolism Liver - pathology Liver Circulation - drug effects Liver, biliary tract, pancreas, portal circulation, spleen Medical sciences Nitrates - blood Nitric Oxide Synthase - antagonists & inhibitors Nitric Oxide Synthase - metabolism Nitric Oxide Synthase Type II Nitric Oxide Synthase Type III Nitrites - blood Reperfusion Injury - pathology Reperfusion Injury - physiopathology Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases Surgery of the digestive system Survival Analysis Swine Thrombosis - prevention & control Tissue Distribution Tyrosine - analogs & derivatives Tyrosine - metabolism |
| title | A novel inhibitor of inducible nitric oxide synthase (ONO-1714) prevents critical warm ischemia-reperfusion injury in the pig liver |
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