Edaravone, a Radical Scavenger, May Enhance or Produce Antiproliferative Effects of Fluvastatin, Amlodipine, Ozagrel, GF109203X and Y27632 on Cultured Basilar Artery Smooth Muscle Cells
Proliferation of vascular smooth muscle cells stimulated by reactive oxygen species (ROS) may play a pivotal role in the pathogenesis of atherosclerosis. To clarify mechanisms by which ROS promote vascular atherogenesis, effects of fluvastatin, amlodipine, ozagrel (thromboxane synthetase inhibitor),...
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| Veröffentlicht in: | Biological & Pharmaceutical Bulletin 2003, Vol.26(12), pp.1706-1710 |
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| creator | Yamaguchi, Tomoaki Oishi, Kazuhiko Uchida, Masaatsu Echizen, Hirotoshi |
| description | Proliferation of vascular smooth muscle cells stimulated by reactive oxygen species (ROS) may play a pivotal role in the pathogenesis of atherosclerosis. To clarify mechanisms by which ROS promote vascular atherogenesis, effects of fluvastatin, amlodipine, ozagrel (thromboxane synthetase inhibitor), GF109203X (a protein kinase C inhibitor) and Y27632 (a ROCK inhibitor) on the proliferation of guinea-pig basilar artery smooth muscle cells (GBa-SM3) in a 5% FBS culture medium were studied over 3 d in the presence or absence of a free radical scavenger, edaravone. Viability of cells at the end of incubation was measured by the 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) test. Results demonstrated that fluvastatin and amlodipine by themselves possess antiproliferative effects on the GBa-SM3 cells at 10—100 μM and 0.1—1 μM, respectively. While edaravone possessed no antiproliferative effect by itself at 100 μM, it significantly (p |
| doi_str_mv | 10.1248/bpb.26.1706 |
| format | Article |
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To clarify mechanisms by which ROS promote vascular atherogenesis, effects of fluvastatin, amlodipine, ozagrel (thromboxane synthetase inhibitor), GF109203X (a protein kinase C inhibitor) and Y27632 (a ROCK inhibitor) on the proliferation of guinea-pig basilar artery smooth muscle cells (GBa-SM3) in a 5% FBS culture medium were studied over 3 d in the presence or absence of a free radical scavenger, edaravone. Viability of cells at the end of incubation was measured by the 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) test. Results demonstrated that fluvastatin and amlodipine by themselves possess antiproliferative effects on the GBa-SM3 cells at 10—100 μM and 0.1—1 μM, respectively. While edaravone possessed no antiproliferative effect by itself at 100 μM, it significantly (p<0.05) augmented the antiproliferative effects of fluvastatin and amlodipine. In addition, ozagrel, GF109203X and Y27632 possessed no appreciable effects on the cell growth by themselves. However, coincubation of edaravone at 100 μM with these agents elicited significant antiproliferative effects for ozagrel, GF109203X and Y27632 at 10—100 μM, 1—10 μM and 0.1—1 μM, respectively. In conclusion, edaravone may have clinically beneficial interactions with fluvastatin, amlodipine and ozagrel regarding the prevention of vascular atherosclerosis. The interactions between edaravone and the inhibitors of protein kinase C and ROCK were suggestive of possible contributions of ROS-triggered intracellular signals associated with these enzymes to vascular atherogenesis, but further studies are required for confirmation.</description><identifier>ISSN: 0918-6158</identifier><identifier>EISSN: 1347-5215</identifier><identifier>DOI: 10.1248/bpb.26.1706</identifier><identifier>PMID: 14646175</identifier><language>eng</language><publisher>Tokyo: The Pharmaceutical Society of Japan</publisher><subject>Amides - pharmacology ; amlodipine ; Amlodipine - pharmacology ; Animals ; Antipyrine - analogs & derivatives ; Antipyrine - pharmacology ; Arteriosclerosis - etiology ; Arteriosclerosis - metabolism ; atherosclerosis ; Basilar Artery - cytology ; Basilar Artery - drug effects ; basilar artery smooth muscle cell ; Biological and medical sciences ; Cardiovascular system ; Cell Division - drug effects ; Cell Division - physiology ; Cell Survival - drug effects ; Cell Survival - physiology ; Cells, Cultured ; Drug Synergism ; Drug Therapy, Combination ; Edaravone ; Enzyme Inhibitors - pharmacology ; Fatty Acids, Monounsaturated - pharmacology ; Fluvastatin ; free radical ; Free Radical Scavengers - pharmacology ; Indoles - pharmacology ; Maleimides - pharmacology ; Medical sciences ; Methacrylates - pharmacology ; Muscle, Smooth, Vascular - cytology ; Muscle, Smooth, Vascular - drug effects ; Muscle, Smooth, Vascular - physiology ; Pharmacology. Drug treatments ; Pyridines - pharmacology ; Reactive Oxygen Species - adverse effects ; Reactive Oxygen Species - pharmacology ; Signal Transduction - drug effects ; Signal Transduction - physiology ; Tetrazolium Salts ; Thiazoles ; Vascular wall</subject><ispartof>Biological and Pharmaceutical Bulletin, 2003, Vol.26(12), pp.1706-1710</ispartof><rights>2003 The Pharmaceutical Society of Japan</rights><rights>2004 INIST-CNRS</rights><rights>Copyright Japan Science and Technology Agency 2003</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c721t-3add28ed065d86d7217cfc7050571e7960cb2568a58879862633203b467c019e3</citedby><cites>FETCH-LOGICAL-c721t-3add28ed065d86d7217cfc7050571e7960cb2568a58879862633203b467c019e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,1883,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=15407764$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14646175$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yamaguchi, Tomoaki</creatorcontrib><creatorcontrib>Oishi, Kazuhiko</creatorcontrib><creatorcontrib>Uchida, Masaatsu</creatorcontrib><creatorcontrib>Echizen, Hirotoshi</creatorcontrib><creatorcontrib>Nakano General Hospital</creatorcontrib><creatorcontrib>Meiji Pharmaceutical University</creatorcontrib><creatorcontrib>cDepartment of Pharmacotherapy</creatorcontrib><creatorcontrib>aDepartment of Hospital Pharmacy</creatorcontrib><creatorcontrib>bDepartments of Pharmacology</creatorcontrib><title>Edaravone, a Radical Scavenger, May Enhance or Produce Antiproliferative Effects of Fluvastatin, Amlodipine, Ozagrel, GF109203X and Y27632 on Cultured Basilar Artery Smooth Muscle Cells</title><title>Biological & Pharmaceutical Bulletin</title><addtitle>Biol Pharm Bull</addtitle><description>Proliferation of vascular smooth muscle cells stimulated by reactive oxygen species (ROS) may play a pivotal role in the pathogenesis of atherosclerosis. To clarify mechanisms by which ROS promote vascular atherogenesis, effects of fluvastatin, amlodipine, ozagrel (thromboxane synthetase inhibitor), GF109203X (a protein kinase C inhibitor) and Y27632 (a ROCK inhibitor) on the proliferation of guinea-pig basilar artery smooth muscle cells (GBa-SM3) in a 5% FBS culture medium were studied over 3 d in the presence or absence of a free radical scavenger, edaravone. Viability of cells at the end of incubation was measured by the 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) test. Results demonstrated that fluvastatin and amlodipine by themselves possess antiproliferative effects on the GBa-SM3 cells at 10—100 μM and 0.1—1 μM, respectively. While edaravone possessed no antiproliferative effect by itself at 100 μM, it significantly (p<0.05) augmented the antiproliferative effects of fluvastatin and amlodipine. In addition, ozagrel, GF109203X and Y27632 possessed no appreciable effects on the cell growth by themselves. However, coincubation of edaravone at 100 μM with these agents elicited significant antiproliferative effects for ozagrel, GF109203X and Y27632 at 10—100 μM, 1—10 μM and 0.1—1 μM, respectively. In conclusion, edaravone may have clinically beneficial interactions with fluvastatin, amlodipine and ozagrel regarding the prevention of vascular atherosclerosis. The interactions between edaravone and the inhibitors of protein kinase C and ROCK were suggestive of possible contributions of ROS-triggered intracellular signals associated with these enzymes to vascular atherogenesis, but further studies are required for confirmation.</description><subject>Amides - pharmacology</subject><subject>amlodipine</subject><subject>Amlodipine - pharmacology</subject><subject>Animals</subject><subject>Antipyrine - analogs & derivatives</subject><subject>Antipyrine - pharmacology</subject><subject>Arteriosclerosis - etiology</subject><subject>Arteriosclerosis - metabolism</subject><subject>atherosclerosis</subject><subject>Basilar Artery - cytology</subject><subject>Basilar Artery - drug effects</subject><subject>basilar artery smooth muscle cell</subject><subject>Biological and medical sciences</subject><subject>Cardiovascular system</subject><subject>Cell Division - drug effects</subject><subject>Cell Division - physiology</subject><subject>Cell Survival - drug effects</subject><subject>Cell Survival - physiology</subject><subject>Cells, Cultured</subject><subject>Drug Synergism</subject><subject>Drug Therapy, Combination</subject><subject>Edaravone</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Fatty Acids, Monounsaturated - pharmacology</subject><subject>Fluvastatin</subject><subject>free radical</subject><subject>Free Radical Scavengers - pharmacology</subject><subject>Indoles - pharmacology</subject><subject>Maleimides - pharmacology</subject><subject>Medical sciences</subject><subject>Methacrylates - pharmacology</subject><subject>Muscle, Smooth, Vascular - cytology</subject><subject>Muscle, Smooth, Vascular - drug effects</subject><subject>Muscle, Smooth, Vascular - physiology</subject><subject>Pharmacology. Drug treatments</subject><subject>Pyridines - pharmacology</subject><subject>Reactive Oxygen Species - adverse effects</subject><subject>Reactive Oxygen Species - pharmacology</subject><subject>Signal Transduction - drug effects</subject><subject>Signal Transduction - physiology</subject><subject>Tetrazolium Salts</subject><subject>Thiazoles</subject><subject>Vascular wall</subject><issn>0918-6158</issn><issn>1347-5215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkVGPEyEUhSdG49bqk--GxPhkWy8wwMxjt2mryW7WuJroE2GAaaehQ4WZJt1_tv9Ouq3bFyCXj3MP92TZewwTTPLiS7WrJoRPsAD-IhtgmosxI5i9zAZQ4mLMMSuusjcxbgBAAKGvsyuc85xjwQbZ49yooPa-tSOk0A9lGq0cutdqb9uVDSN0qw5o3q5Vqy3yAX0P3vTpOG27Zhe8a2obVNfsLZrXtdVdRL5GC9fvVexSvR2h6dZ50-yaY4e7B7UK1o3QcoGhJEB_I9Ua9IcITgnyLZr1ruuDNehaxcapgKahs-GA7rfed2t020ftLJpZ5-Lb7FWtXLTvzvsw-7WY_5x9Hd_cLb_NpjdjLQjuxlQZQwprgDNTcJNqQtdaAAMmsBUlB10RxgvFikKUBSec0mSsyrnQgEtLh9nHk2767t_exk5ufB_a1FLiPC8pKfP0ZJh9PlE6-BiDreUuNFsVDhKDPMYkU0yScHmMKdEfzpp9tbXmwp5zScCnM6BiCqQOaf5NvHAsByF4nrjliUsqx-R869KgLw51FFXjnZcEgEoAwjGRgOmTjbRgwCAY40dL1yelTQpuZZ9bqdA1aebP9sl5fRL4f6nXKkjb0n_aA8ZA</recordid><startdate>20031201</startdate><enddate>20031201</enddate><creator>Yamaguchi, Tomoaki</creator><creator>Oishi, Kazuhiko</creator><creator>Uchida, Masaatsu</creator><creator>Echizen, Hirotoshi</creator><general>The Pharmaceutical Society of Japan</general><general>Pharmaceutical Society of Japan</general><general>Maruzen</general><general>Japan Science and Technology Agency</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>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope></search><sort><creationdate>20031201</creationdate><title>Edaravone, a Radical Scavenger, May Enhance or Produce Antiproliferative Effects of Fluvastatin, Amlodipine, Ozagrel, GF109203X and Y27632 on Cultured Basilar Artery Smooth Muscle Cells</title><author>Yamaguchi, Tomoaki ; Oishi, Kazuhiko ; Uchida, Masaatsu ; Echizen, Hirotoshi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c721t-3add28ed065d86d7217cfc7050571e7960cb2568a58879862633203b467c019e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Amides - pharmacology</topic><topic>amlodipine</topic><topic>Amlodipine - pharmacology</topic><topic>Animals</topic><topic>Antipyrine - analogs & derivatives</topic><topic>Antipyrine - pharmacology</topic><topic>Arteriosclerosis - etiology</topic><topic>Arteriosclerosis - metabolism</topic><topic>atherosclerosis</topic><topic>Basilar Artery - cytology</topic><topic>Basilar Artery - drug effects</topic><topic>basilar artery smooth muscle cell</topic><topic>Biological and medical sciences</topic><topic>Cardiovascular system</topic><topic>Cell Division - drug effects</topic><topic>Cell Division - physiology</topic><topic>Cell Survival - drug effects</topic><topic>Cell Survival - physiology</topic><topic>Cells, Cultured</topic><topic>Drug Synergism</topic><topic>Drug Therapy, Combination</topic><topic>Edaravone</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Fatty Acids, Monounsaturated - pharmacology</topic><topic>Fluvastatin</topic><topic>free radical</topic><topic>Free Radical Scavengers - pharmacology</topic><topic>Indoles - pharmacology</topic><topic>Maleimides - pharmacology</topic><topic>Medical sciences</topic><topic>Methacrylates - pharmacology</topic><topic>Muscle, Smooth, Vascular - cytology</topic><topic>Muscle, Smooth, Vascular - drug effects</topic><topic>Muscle, Smooth, Vascular - physiology</topic><topic>Pharmacology. Drug treatments</topic><topic>Pyridines - pharmacology</topic><topic>Reactive Oxygen Species - adverse effects</topic><topic>Reactive Oxygen Species - pharmacology</topic><topic>Signal Transduction - drug effects</topic><topic>Signal Transduction - physiology</topic><topic>Tetrazolium Salts</topic><topic>Thiazoles</topic><topic>Vascular wall</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yamaguchi, Tomoaki</creatorcontrib><creatorcontrib>Oishi, Kazuhiko</creatorcontrib><creatorcontrib>Uchida, Masaatsu</creatorcontrib><creatorcontrib>Echizen, Hirotoshi</creatorcontrib><creatorcontrib>Nakano General Hospital</creatorcontrib><creatorcontrib>Meiji Pharmaceutical University</creatorcontrib><creatorcontrib>cDepartment of Pharmacotherapy</creatorcontrib><creatorcontrib>aDepartment of Hospital Pharmacy</creatorcontrib><creatorcontrib>bDepartments of Pharmacology</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>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Biological & Pharmaceutical Bulletin</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yamaguchi, Tomoaki</au><au>Oishi, Kazuhiko</au><au>Uchida, Masaatsu</au><au>Echizen, Hirotoshi</au><aucorp>Nakano General Hospital</aucorp><aucorp>Meiji Pharmaceutical University</aucorp><aucorp>cDepartment of Pharmacotherapy</aucorp><aucorp>aDepartment of Hospital Pharmacy</aucorp><aucorp>bDepartments of Pharmacology</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Edaravone, a Radical Scavenger, May Enhance or Produce Antiproliferative Effects of Fluvastatin, Amlodipine, Ozagrel, GF109203X and Y27632 on Cultured Basilar Artery Smooth Muscle Cells</atitle><jtitle>Biological & Pharmaceutical Bulletin</jtitle><addtitle>Biol Pharm Bull</addtitle><date>2003-12-01</date><risdate>2003</risdate><volume>26</volume><issue>12</issue><spage>1706</spage><epage>1710</epage><pages>1706-1710</pages><issn>0918-6158</issn><eissn>1347-5215</eissn><abstract>Proliferation of vascular smooth muscle cells stimulated by reactive oxygen species (ROS) may play a pivotal role in the pathogenesis of atherosclerosis. To clarify mechanisms by which ROS promote vascular atherogenesis, effects of fluvastatin, amlodipine, ozagrel (thromboxane synthetase inhibitor), GF109203X (a protein kinase C inhibitor) and Y27632 (a ROCK inhibitor) on the proliferation of guinea-pig basilar artery smooth muscle cells (GBa-SM3) in a 5% FBS culture medium were studied over 3 d in the presence or absence of a free radical scavenger, edaravone. Viability of cells at the end of incubation was measured by the 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) test. Results demonstrated that fluvastatin and amlodipine by themselves possess antiproliferative effects on the GBa-SM3 cells at 10—100 μM and 0.1—1 μM, respectively. While edaravone possessed no antiproliferative effect by itself at 100 μM, it significantly (p<0.05) augmented the antiproliferative effects of fluvastatin and amlodipine. In addition, ozagrel, GF109203X and Y27632 possessed no appreciable effects on the cell growth by themselves. However, coincubation of edaravone at 100 μM with these agents elicited significant antiproliferative effects for ozagrel, GF109203X and Y27632 at 10—100 μM, 1—10 μM and 0.1—1 μM, respectively. In conclusion, edaravone may have clinically beneficial interactions with fluvastatin, amlodipine and ozagrel regarding the prevention of vascular atherosclerosis. The interactions between edaravone and the inhibitors of protein kinase C and ROCK were suggestive of possible contributions of ROS-triggered intracellular signals associated with these enzymes to vascular atherogenesis, but further studies are required for confirmation.</abstract><cop>Tokyo</cop><pub>The Pharmaceutical Society of Japan</pub><pmid>14646175</pmid><doi>10.1248/bpb.26.1706</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Biological and Pharmaceutical Bulletin, 2003, Vol.26(12), pp.1706-1710 |
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| source | MEDLINE; J-STAGE (Japan Science & Technology Information Aggregator, Electronic) Freely Available Titles - Japanese; EZB-FREE-00999 freely available EZB journals; Free Full-Text Journals in Chemistry |
| subjects | Amides - pharmacology amlodipine Amlodipine - pharmacology Animals Antipyrine - analogs & derivatives Antipyrine - pharmacology Arteriosclerosis - etiology Arteriosclerosis - metabolism atherosclerosis Basilar Artery - cytology Basilar Artery - drug effects basilar artery smooth muscle cell Biological and medical sciences Cardiovascular system Cell Division - drug effects Cell Division - physiology Cell Survival - drug effects Cell Survival - physiology Cells, Cultured Drug Synergism Drug Therapy, Combination Edaravone Enzyme Inhibitors - pharmacology Fatty Acids, Monounsaturated - pharmacology Fluvastatin free radical Free Radical Scavengers - pharmacology Indoles - pharmacology Maleimides - pharmacology Medical sciences Methacrylates - pharmacology Muscle, Smooth, Vascular - cytology Muscle, Smooth, Vascular - drug effects Muscle, Smooth, Vascular - physiology Pharmacology. Drug treatments Pyridines - pharmacology Reactive Oxygen Species - adverse effects Reactive Oxygen Species - pharmacology Signal Transduction - drug effects Signal Transduction - physiology Tetrazolium Salts Thiazoles Vascular wall |
| title | Edaravone, a Radical Scavenger, May Enhance or Produce Antiproliferative Effects of Fluvastatin, Amlodipine, Ozagrel, GF109203X and Y27632 on Cultured Basilar Artery Smooth Muscle Cells |
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