MCI-186 reduces oxidative cellular damage and increases DNA repair function in the rabbit spinal cord after transient ischemia
Paraplegia is a serious complication of operations on the thoracic and thoracoabdominal aorta. To investigate the mechanism by which motor neurons are damaged during these operations, we have reported a rabbit model of spinal cord ischemia. We also tested whether a free radical scavenger MCI-186 tha...
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| Veröffentlicht in: | The Annals of thoracic surgery 2004-08, Vol.78 (2), p.602-607 |
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| creator | Takahashi, Goro Sakurai, Masahiro Abe, Koji Itoyama, Yasuto Tabayashi, Koichi |
| description | Paraplegia is a serious complication of operations on the thoracic and thoracoabdominal aorta. To investigate the mechanism by which motor neurons are damaged during these operations, we have reported a rabbit model of spinal cord ischemia. We also tested whether a free radical scavenger MCI-186 that is useful for treating ischemic damage in the brain can protect against ischemic spinal cord damage.
Fifteen minutes of ischemia was induced, then MCI-186 or vehicle was injected intravenously. Cell damage was analyzed by observing the function of the lower limbs and by counting the number of motor neurons. To investigate the mechanism by which MCI-186 prevents ischemic spinal cord damage, we observed the immunoreactivity of 8-hydroxy-2'-deoxyguanosine as an oxidative DNA damage marker and redox effector as a DNA repair marker.
In sham control, 8-hydroxy-2'-deoxyguanosine was not observed, and the nuclear expression of redox effector was observed. In vehicle injection group (group I), the nuclear expression of 8-hydroxy-2'-deoxyguanosine was observed at 1 and 2 days after reperfusion. The nuclear expression of redox effector was observed at 8 hours and 1 day, and disappeared at 2 days after transient ischemia. In MCI-186 injection group (group M), the nuclear expression of 8-hydroxy-2'-deoxyguanosine was not observed, and redox effector was observed at 8 hours and 1 and 2 days.
These results suggest that redox effector decreased in motor neurons after transient ischemia and this reduction preceded oxidative DNA damage. MCI-186 works as a radical scavenger and reduced oxidative DNA damage, so redox effector did not disappear. MCI-186 could be a strong candidate for a use as a therapeutic agent in the treatment of ischemic spinal cord injury. |
| doi_str_mv | 10.1016/j.athoracsur.2004.02.133 |
| format | Article |
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Fifteen minutes of ischemia was induced, then MCI-186 or vehicle was injected intravenously. Cell damage was analyzed by observing the function of the lower limbs and by counting the number of motor neurons. To investigate the mechanism by which MCI-186 prevents ischemic spinal cord damage, we observed the immunoreactivity of 8-hydroxy-2'-deoxyguanosine as an oxidative DNA damage marker and redox effector as a DNA repair marker.
In sham control, 8-hydroxy-2'-deoxyguanosine was not observed, and the nuclear expression of redox effector was observed. In vehicle injection group (group I), the nuclear expression of 8-hydroxy-2'-deoxyguanosine was observed at 1 and 2 days after reperfusion. The nuclear expression of redox effector was observed at 8 hours and 1 day, and disappeared at 2 days after transient ischemia. In MCI-186 injection group (group M), the nuclear expression of 8-hydroxy-2'-deoxyguanosine was not observed, and redox effector was observed at 8 hours and 1 and 2 days.
These results suggest that redox effector decreased in motor neurons after transient ischemia and this reduction preceded oxidative DNA damage. MCI-186 works as a radical scavenger and reduced oxidative DNA damage, so redox effector did not disappear. MCI-186 could be a strong candidate for a use as a therapeutic agent in the treatment of ischemic spinal cord injury.</description><identifier>ISSN: 0003-4975</identifier><identifier>EISSN: 1552-6259</identifier><identifier>DOI: 10.1016/j.athoracsur.2004.02.133</identifier><identifier>PMID: 15276530</identifier><identifier>CODEN: ATHSAK</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Animals ; Antipyrine - analogs & derivatives ; Antipyrine - pharmacology ; Antipyrine - therapeutic use ; Apoptosis - drug effects ; Ataxia - etiology ; Ataxia - prevention & control ; Biological and medical sciences ; Biomarkers ; Cardiology. Vascular system ; Cell Count ; Cell Nucleus - chemistry ; Deoxyguanosine - analogs & derivatives ; Deoxyguanosine - analysis ; DNA Damage ; DNA Repair - drug effects ; DNA-(Apurinic or Apyrimidinic Site) Lyase - analysis ; Free Radical Scavengers - pharmacology ; Free Radical Scavengers - therapeutic use ; Ischemia - drug therapy ; Ischemia - metabolism ; Ischemia - pathology ; Male ; Medical sciences ; Models, Animal ; Motor Neurons - chemistry ; Motor Neurons - drug effects ; Motor Neurons - pathology ; Motor Neurons - ultrastructure ; Nerve Tissue Proteins - analysis ; Oxidation-Reduction ; Oxidative Stress - drug effects ; Paraplegia - etiology ; Paraplegia - prevention & control ; Pneumology ; Postoperative Complications - etiology ; Postoperative Complications - prevention & control ; Rabbits ; Spinal Cord - blood supply</subject><ispartof>The Annals of thoracic surgery, 2004-08, Vol.78 (2), p.602-607</ispartof><rights>2004 The Society of Thoracic Surgeons</rights><rights>2004 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c435t-b6b48d1bf395d823a52f24e7401b57d12c25c3252b052c5127675323326593c43</citedby><cites>FETCH-LOGICAL-c435t-b6b48d1bf395d823a52f24e7401b57d12c25c3252b052c5127675323326593c43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0003497504006964$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16015688$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15276530$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Takahashi, Goro</creatorcontrib><creatorcontrib>Sakurai, Masahiro</creatorcontrib><creatorcontrib>Abe, Koji</creatorcontrib><creatorcontrib>Itoyama, Yasuto</creatorcontrib><creatorcontrib>Tabayashi, Koichi</creatorcontrib><title>MCI-186 reduces oxidative cellular damage and increases DNA repair function in the rabbit spinal cord after transient ischemia</title><title>The Annals of thoracic surgery</title><addtitle>Ann Thorac Surg</addtitle><description>Paraplegia is a serious complication of operations on the thoracic and thoracoabdominal aorta. To investigate the mechanism by which motor neurons are damaged during these operations, we have reported a rabbit model of spinal cord ischemia. We also tested whether a free radical scavenger MCI-186 that is useful for treating ischemic damage in the brain can protect against ischemic spinal cord damage.
Fifteen minutes of ischemia was induced, then MCI-186 or vehicle was injected intravenously. Cell damage was analyzed by observing the function of the lower limbs and by counting the number of motor neurons. To investigate the mechanism by which MCI-186 prevents ischemic spinal cord damage, we observed the immunoreactivity of 8-hydroxy-2'-deoxyguanosine as an oxidative DNA damage marker and redox effector as a DNA repair marker.
In sham control, 8-hydroxy-2'-deoxyguanosine was not observed, and the nuclear expression of redox effector was observed. In vehicle injection group (group I), the nuclear expression of 8-hydroxy-2'-deoxyguanosine was observed at 1 and 2 days after reperfusion. The nuclear expression of redox effector was observed at 8 hours and 1 day, and disappeared at 2 days after transient ischemia. In MCI-186 injection group (group M), the nuclear expression of 8-hydroxy-2'-deoxyguanosine was not observed, and redox effector was observed at 8 hours and 1 and 2 days.
These results suggest that redox effector decreased in motor neurons after transient ischemia and this reduction preceded oxidative DNA damage. MCI-186 works as a radical scavenger and reduced oxidative DNA damage, so redox effector did not disappear. MCI-186 could be a strong candidate for a use as a therapeutic agent in the treatment of ischemic spinal cord injury.</description><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Animals</subject><subject>Antipyrine - analogs & derivatives</subject><subject>Antipyrine - pharmacology</subject><subject>Antipyrine - therapeutic use</subject><subject>Apoptosis - drug effects</subject><subject>Ataxia - etiology</subject><subject>Ataxia - prevention & control</subject><subject>Biological and medical sciences</subject><subject>Biomarkers</subject><subject>Cardiology. Vascular system</subject><subject>Cell Count</subject><subject>Cell Nucleus - chemistry</subject><subject>Deoxyguanosine - analogs & derivatives</subject><subject>Deoxyguanosine - analysis</subject><subject>DNA Damage</subject><subject>DNA Repair - drug effects</subject><subject>DNA-(Apurinic or Apyrimidinic Site) Lyase - analysis</subject><subject>Free Radical Scavengers - pharmacology</subject><subject>Free Radical Scavengers - therapeutic use</subject><subject>Ischemia - drug therapy</subject><subject>Ischemia - metabolism</subject><subject>Ischemia - pathology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Models, Animal</subject><subject>Motor Neurons - chemistry</subject><subject>Motor Neurons - drug effects</subject><subject>Motor Neurons - pathology</subject><subject>Motor Neurons - ultrastructure</subject><subject>Nerve Tissue Proteins - analysis</subject><subject>Oxidation-Reduction</subject><subject>Oxidative Stress - drug effects</subject><subject>Paraplegia - etiology</subject><subject>Paraplegia - prevention & control</subject><subject>Pneumology</subject><subject>Postoperative Complications - etiology</subject><subject>Postoperative Complications - prevention & control</subject><subject>Rabbits</subject><subject>Spinal Cord - blood supply</subject><issn>0003-4975</issn><issn>1552-6259</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE2P0zAQhi0EYsvCX0C-wC3BH7GTHJcuHystcIGzNbEn1FWaFNtZwYXfzqxaqUdO1miedzzzMMalqKWQ9t2-hrJbEvi8ploJ0dRC1VLrJ2wjjVGVVaZ_yjZCCF01fWuu2Iuc91Qqaj9nV9Ko1hotNuzvl-1dJTvLE4bVY-bL7xigxAfkHqdpnSDxAAf4iRzmwOPsE0Im7vbrDWWOEBMf19mXuMzU5WWHPMEwxMLzMc4wcb-kwGEsmHhJMOeIc-Ex-x0eIrxkz0aYMr46v9fsx8cP37efq_tvn-62N_eVb7Qp1WCHpgtyGHVvQqc0GDWqBttGyMG0QSqvjNfKqEEY5Y2k61qjldbKml7TjGv29jT3mJZfK-biDrQCHQgzLmt21tKsXvcEdifQpyXnhKM7pniA9MdJ4R7du727uHeP7p1QjtxT9PX5j3U4YLgEz7IJeHMGIHuYRrLhY75wVkhju4649ycOychDxOSyJ2seQ0zoiwtL_P82_wArPacU</recordid><startdate>20040801</startdate><enddate>20040801</enddate><creator>Takahashi, Goro</creator><creator>Sakurai, Masahiro</creator><creator>Abe, Koji</creator><creator>Itoyama, Yasuto</creator><creator>Tabayashi, Koichi</creator><general>Elsevier Inc</general><general>Elsevier Science</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>7X8</scope></search><sort><creationdate>20040801</creationdate><title>MCI-186 reduces oxidative cellular damage and increases DNA repair function in the rabbit spinal cord after transient ischemia</title><author>Takahashi, Goro ; Sakurai, Masahiro ; Abe, Koji ; Itoyama, Yasuto ; Tabayashi, Koichi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c435t-b6b48d1bf395d823a52f24e7401b57d12c25c3252b052c5127675323326593c43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</topic><topic>Animals</topic><topic>Antipyrine - analogs & derivatives</topic><topic>Antipyrine - pharmacology</topic><topic>Antipyrine - therapeutic use</topic><topic>Apoptosis - drug effects</topic><topic>Ataxia - etiology</topic><topic>Ataxia - prevention & control</topic><topic>Biological and medical sciences</topic><topic>Biomarkers</topic><topic>Cardiology. Vascular system</topic><topic>Cell Count</topic><topic>Cell Nucleus - chemistry</topic><topic>Deoxyguanosine - analogs & derivatives</topic><topic>Deoxyguanosine - analysis</topic><topic>DNA Damage</topic><topic>DNA Repair - drug effects</topic><topic>DNA-(Apurinic or Apyrimidinic Site) Lyase - analysis</topic><topic>Free Radical Scavengers - pharmacology</topic><topic>Free Radical Scavengers - therapeutic use</topic><topic>Ischemia - drug therapy</topic><topic>Ischemia - metabolism</topic><topic>Ischemia - pathology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Models, Animal</topic><topic>Motor Neurons - chemistry</topic><topic>Motor Neurons - drug effects</topic><topic>Motor Neurons - pathology</topic><topic>Motor Neurons - ultrastructure</topic><topic>Nerve Tissue Proteins - analysis</topic><topic>Oxidation-Reduction</topic><topic>Oxidative Stress - drug effects</topic><topic>Paraplegia - etiology</topic><topic>Paraplegia - prevention & control</topic><topic>Pneumology</topic><topic>Postoperative Complications - etiology</topic><topic>Postoperative Complications - prevention & control</topic><topic>Rabbits</topic><topic>Spinal Cord - blood supply</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Takahashi, Goro</creatorcontrib><creatorcontrib>Sakurai, Masahiro</creatorcontrib><creatorcontrib>Abe, Koji</creatorcontrib><creatorcontrib>Itoyama, Yasuto</creatorcontrib><creatorcontrib>Tabayashi, 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>MEDLINE - Academic</collection><jtitle>The Annals of thoracic surgery</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Takahashi, Goro</au><au>Sakurai, Masahiro</au><au>Abe, Koji</au><au>Itoyama, Yasuto</au><au>Tabayashi, Koichi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MCI-186 reduces oxidative cellular damage and increases DNA repair function in the rabbit spinal cord after transient ischemia</atitle><jtitle>The Annals of thoracic surgery</jtitle><addtitle>Ann Thorac Surg</addtitle><date>2004-08-01</date><risdate>2004</risdate><volume>78</volume><issue>2</issue><spage>602</spage><epage>607</epage><pages>602-607</pages><issn>0003-4975</issn><eissn>1552-6259</eissn><coden>ATHSAK</coden><abstract>Paraplegia is a serious complication of operations on the thoracic and thoracoabdominal aorta. To investigate the mechanism by which motor neurons are damaged during these operations, we have reported a rabbit model of spinal cord ischemia. We also tested whether a free radical scavenger MCI-186 that is useful for treating ischemic damage in the brain can protect against ischemic spinal cord damage.
Fifteen minutes of ischemia was induced, then MCI-186 or vehicle was injected intravenously. Cell damage was analyzed by observing the function of the lower limbs and by counting the number of motor neurons. To investigate the mechanism by which MCI-186 prevents ischemic spinal cord damage, we observed the immunoreactivity of 8-hydroxy-2'-deoxyguanosine as an oxidative DNA damage marker and redox effector as a DNA repair marker.
In sham control, 8-hydroxy-2'-deoxyguanosine was not observed, and the nuclear expression of redox effector was observed. In vehicle injection group (group I), the nuclear expression of 8-hydroxy-2'-deoxyguanosine was observed at 1 and 2 days after reperfusion. The nuclear expression of redox effector was observed at 8 hours and 1 day, and disappeared at 2 days after transient ischemia. In MCI-186 injection group (group M), the nuclear expression of 8-hydroxy-2'-deoxyguanosine was not observed, and redox effector was observed at 8 hours and 1 and 2 days.
These results suggest that redox effector decreased in motor neurons after transient ischemia and this reduction preceded oxidative DNA damage. MCI-186 works as a radical scavenger and reduced oxidative DNA damage, so redox effector did not disappear. MCI-186 could be a strong candidate for a use as a therapeutic agent in the treatment of ischemic spinal cord injury.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>15276530</pmid><doi>10.1016/j.athoracsur.2004.02.133</doi><tpages>6</tpages></addata></record> |
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| subjects | Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Animals Antipyrine - analogs & derivatives Antipyrine - pharmacology Antipyrine - therapeutic use Apoptosis - drug effects Ataxia - etiology Ataxia - prevention & control Biological and medical sciences Biomarkers Cardiology. Vascular system Cell Count Cell Nucleus - chemistry Deoxyguanosine - analogs & derivatives Deoxyguanosine - analysis DNA Damage DNA Repair - drug effects DNA-(Apurinic or Apyrimidinic Site) Lyase - analysis Free Radical Scavengers - pharmacology Free Radical Scavengers - therapeutic use Ischemia - drug therapy Ischemia - metabolism Ischemia - pathology Male Medical sciences Models, Animal Motor Neurons - chemistry Motor Neurons - drug effects Motor Neurons - pathology Motor Neurons - ultrastructure Nerve Tissue Proteins - analysis Oxidation-Reduction Oxidative Stress - drug effects Paraplegia - etiology Paraplegia - prevention & control Pneumology Postoperative Complications - etiology Postoperative Complications - prevention & control Rabbits Spinal Cord - blood supply |
| title | MCI-186 reduces oxidative cellular damage and increases DNA repair function in the rabbit spinal cord after transient ischemia |
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