Hypolipidemic effects of NB-598 in dogs
NB-598, a new inhibitor of mammalian squalene epoxidase, was found to be a potent inhibitor of microsomal squalene epoxidase from dog liver. Hypolipidemic effects of NB-598 were compared with those of simvastatin (MK-733, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor) in dogs. NB-598 w...
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| Veröffentlicht in: | Atherosclerosis 1991-06, Vol.88 (2), p.183-192 |
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| container_title | Atherosclerosis |
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| creator | Horie, Masahiro Sawasaki, Yoshio Fukuzumi, Hitoshi Watanabe, Keiko Iizuka, Yuri Tsuchiya, Yoshimi Kamei, Toshio |
| description | NB-598, a new inhibitor of mammalian squalene epoxidase, was found to be a potent inhibitor of microsomal squalene epoxidase from dog liver. Hypolipidemic effects of NB-598 were compared with those of simvastatin (MK-733, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor) in dogs. NB-598 was found to decrease serum total cholesterol levels and increase serum squalene levels in a dose-dependent manner. MK-733 decreased serum total cholesterol and squalene levels. Both NB-598 and MK-733 decreased all classes of lipoprotein cholesterol, and they decreased low density lipoprotein cholesterol most potently. Both drugs decreased phospholipid levels in parallel with cholesterol levels. NB-598 also decreased triacylglycerol levels. After termination of drug administration, these levels returned to the control levels. The potency of NB-598 is thought to be as great or greater than that of MK-733. Moreover, NB-598 increased squalene concentrations in the feces and gallbladder bile, but it did not affect neutral sterol and bile acid concentrations. NB-598 did not affect the lithogenic index. |
| doi_str_mv | 10.1016/0021-9150(91)90080-M |
| format | Article |
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Hypolipidemic effects of NB-598 were compared with those of simvastatin (MK-733, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor) in dogs. NB-598 was found to decrease serum total cholesterol levels and increase serum squalene levels in a dose-dependent manner. MK-733 decreased serum total cholesterol and squalene levels. Both NB-598 and MK-733 decreased all classes of lipoprotein cholesterol, and they decreased low density lipoprotein cholesterol most potently. Both drugs decreased phospholipid levels in parallel with cholesterol levels. NB-598 also decreased triacylglycerol levels. After termination of drug administration, these levels returned to the control levels. The potency of NB-598 is thought to be as great or greater than that of MK-733. Moreover, NB-598 increased squalene concentrations in the feces and gallbladder bile, but it did not affect neutral sterol and bile acid concentrations. NB-598 did not affect the lithogenic index.</description><identifier>ISSN: 0021-9150</identifier><identifier>EISSN: 1879-1484</identifier><identifier>DOI: 10.1016/0021-9150(91)90080-M</identifier><identifier>PMID: 1892485</identifier><language>eng</language><publisher>Amsterdam: Elsevier Ireland Ltd</publisher><subject>Animals ; Anticholesteremic Agents - pharmacology ; Benzylamines - pharmacology ; Bile - metabolism ; Bile acids ; Bile Acids and Salts - metabolism ; Biological and medical sciences ; Cholesterol ; Cholesterol - blood ; Cholesterol - metabolism ; Dog ; Dogs ; Ent. Stomatology ; Feces - chemistry ; Hypolipidemic drug ; Lipids - blood ; Lipoprotein ; Lipoproteins - blood ; Lovastatin - analogs & derivatives ; Lovastatin - pharmacology ; Male ; Medical sciences ; NB-598 ; Oxygenases - antagonists & inhibitors ; Pharmacology. Drug treatments ; Phospholipids - blood ; Simvastatin ; Squalene ; Squalene - blood ; Squalene - metabolism ; Squalene epoxidase inhibitor ; Squalene Monooxygenase ; Thiophenes - pharmacology ; Triglycerides - blood</subject><ispartof>Atherosclerosis, 1991-06, Vol.88 (2), p.183-192</ispartof><rights>1991</rights><rights>1992 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c386t-ecbab68ef04b5af8cdc262e08af387ab18865885f651570533554aa82b5f546c3</citedby><cites>FETCH-LOGICAL-c386t-ecbab68ef04b5af8cdc262e08af387ab18865885f651570533554aa82b5f546c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/002191509190080M$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=5466934$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/1892485$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Horie, Masahiro</creatorcontrib><creatorcontrib>Sawasaki, Yoshio</creatorcontrib><creatorcontrib>Fukuzumi, Hitoshi</creatorcontrib><creatorcontrib>Watanabe, Keiko</creatorcontrib><creatorcontrib>Iizuka, Yuri</creatorcontrib><creatorcontrib>Tsuchiya, Yoshimi</creatorcontrib><creatorcontrib>Kamei, Toshio</creatorcontrib><title>Hypolipidemic effects of NB-598 in dogs</title><title>Atherosclerosis</title><addtitle>Atherosclerosis</addtitle><description>NB-598, a new inhibitor of mammalian squalene epoxidase, was found to be a potent inhibitor of microsomal squalene epoxidase from dog liver. Hypolipidemic effects of NB-598 were compared with those of simvastatin (MK-733, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor) in dogs. NB-598 was found to decrease serum total cholesterol levels and increase serum squalene levels in a dose-dependent manner. MK-733 decreased serum total cholesterol and squalene levels. Both NB-598 and MK-733 decreased all classes of lipoprotein cholesterol, and they decreased low density lipoprotein cholesterol most potently. Both drugs decreased phospholipid levels in parallel with cholesterol levels. NB-598 also decreased triacylglycerol levels. After termination of drug administration, these levels returned to the control levels. The potency of NB-598 is thought to be as great or greater than that of MK-733. Moreover, NB-598 increased squalene concentrations in the feces and gallbladder bile, but it did not affect neutral sterol and bile acid concentrations. NB-598 did not affect the lithogenic index.</description><subject>Animals</subject><subject>Anticholesteremic Agents - pharmacology</subject><subject>Benzylamines - pharmacology</subject><subject>Bile - metabolism</subject><subject>Bile acids</subject><subject>Bile Acids and Salts - metabolism</subject><subject>Biological and medical sciences</subject><subject>Cholesterol</subject><subject>Cholesterol - blood</subject><subject>Cholesterol - metabolism</subject><subject>Dog</subject><subject>Dogs</subject><subject>Ent. Stomatology</subject><subject>Feces - chemistry</subject><subject>Hypolipidemic drug</subject><subject>Lipids - blood</subject><subject>Lipoprotein</subject><subject>Lipoproteins - blood</subject><subject>Lovastatin - analogs & derivatives</subject><subject>Lovastatin - pharmacology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>NB-598</subject><subject>Oxygenases - antagonists & inhibitors</subject><subject>Pharmacology. Drug treatments</subject><subject>Phospholipids - blood</subject><subject>Simvastatin</subject><subject>Squalene</subject><subject>Squalene - blood</subject><subject>Squalene - metabolism</subject><subject>Squalene epoxidase inhibitor</subject><subject>Squalene Monooxygenase</subject><subject>Thiophenes - pharmacology</subject><subject>Triglycerides - blood</subject><issn>0021-9150</issn><issn>1879-1484</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1991</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMtOwzAQRS0EKuXxByBlgXgsAuPEdiYbJKiAIrWwgbXlODYyyou4Rerf45Kq7NjMLObMaO4h5ITCNQUqbgASGueUw2VOr3IAhHi-Q8YUszymDNkuGW-RfXLg_ScAsIziiIwo5glDPiYX01XXVq5zpamdjoy1Ri981Nro5T7mOUauicr2wx-RPasqb443_ZC8Pz68Tabx7PXpeXI3i3WKYhEbXahCoLHACq4s6lInIjGAyqaYqYIiCo7IreCUZ8DTlHOmFCYFt5wJnR6S8-Fu17dfS-MXsnZem6pSjWmXXmYJ5IwCBJANoO5b73tjZde7WvUrSUGu_ch1eLkOH4r89SPnYe10c39Z1Kb8WxqEhPnZZq68VpXtVaOd32LhR5GnLGC3A2aCi29neum1M402peuDQFm27v8_fgC61n4u</recordid><startdate>19910601</startdate><enddate>19910601</enddate><creator>Horie, Masahiro</creator><creator>Sawasaki, Yoshio</creator><creator>Fukuzumi, Hitoshi</creator><creator>Watanabe, Keiko</creator><creator>Iizuka, Yuri</creator><creator>Tsuchiya, Yoshimi</creator><creator>Kamei, Toshio</creator><general>Elsevier Ireland Ltd</general><general>Elsevier</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>19910601</creationdate><title>Hypolipidemic effects of NB-598 in dogs</title><author>Horie, Masahiro ; Sawasaki, Yoshio ; Fukuzumi, Hitoshi ; Watanabe, Keiko ; Iizuka, Yuri ; Tsuchiya, Yoshimi ; Kamei, Toshio</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c386t-ecbab68ef04b5af8cdc262e08af387ab18865885f651570533554aa82b5f546c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1991</creationdate><topic>Animals</topic><topic>Anticholesteremic Agents - pharmacology</topic><topic>Benzylamines - pharmacology</topic><topic>Bile - metabolism</topic><topic>Bile acids</topic><topic>Bile Acids and Salts - metabolism</topic><topic>Biological and medical sciences</topic><topic>Cholesterol</topic><topic>Cholesterol - blood</topic><topic>Cholesterol - metabolism</topic><topic>Dog</topic><topic>Dogs</topic><topic>Ent. Stomatology</topic><topic>Feces - chemistry</topic><topic>Hypolipidemic drug</topic><topic>Lipids - blood</topic><topic>Lipoprotein</topic><topic>Lipoproteins - blood</topic><topic>Lovastatin - analogs & derivatives</topic><topic>Lovastatin - pharmacology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>NB-598</topic><topic>Oxygenases - antagonists & inhibitors</topic><topic>Pharmacology. Drug treatments</topic><topic>Phospholipids - blood</topic><topic>Simvastatin</topic><topic>Squalene</topic><topic>Squalene - blood</topic><topic>Squalene - metabolism</topic><topic>Squalene epoxidase inhibitor</topic><topic>Squalene Monooxygenase</topic><topic>Thiophenes - pharmacology</topic><topic>Triglycerides - blood</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Horie, Masahiro</creatorcontrib><creatorcontrib>Sawasaki, Yoshio</creatorcontrib><creatorcontrib>Fukuzumi, Hitoshi</creatorcontrib><creatorcontrib>Watanabe, Keiko</creatorcontrib><creatorcontrib>Iizuka, Yuri</creatorcontrib><creatorcontrib>Tsuchiya, Yoshimi</creatorcontrib><creatorcontrib>Kamei, Toshio</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>Atherosclerosis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Horie, Masahiro</au><au>Sawasaki, Yoshio</au><au>Fukuzumi, Hitoshi</au><au>Watanabe, Keiko</au><au>Iizuka, Yuri</au><au>Tsuchiya, Yoshimi</au><au>Kamei, Toshio</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hypolipidemic effects of NB-598 in dogs</atitle><jtitle>Atherosclerosis</jtitle><addtitle>Atherosclerosis</addtitle><date>1991-06-01</date><risdate>1991</risdate><volume>88</volume><issue>2</issue><spage>183</spage><epage>192</epage><pages>183-192</pages><issn>0021-9150</issn><eissn>1879-1484</eissn><abstract>NB-598, a new inhibitor of mammalian squalene epoxidase, was found to be a potent inhibitor of microsomal squalene epoxidase from dog liver. Hypolipidemic effects of NB-598 were compared with those of simvastatin (MK-733, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor) in dogs. NB-598 was found to decrease serum total cholesterol levels and increase serum squalene levels in a dose-dependent manner. MK-733 decreased serum total cholesterol and squalene levels. Both NB-598 and MK-733 decreased all classes of lipoprotein cholesterol, and they decreased low density lipoprotein cholesterol most potently. Both drugs decreased phospholipid levels in parallel with cholesterol levels. NB-598 also decreased triacylglycerol levels. After termination of drug administration, these levels returned to the control levels. The potency of NB-598 is thought to be as great or greater than that of MK-733. Moreover, NB-598 increased squalene concentrations in the feces and gallbladder bile, but it did not affect neutral sterol and bile acid concentrations. NB-598 did not affect the lithogenic index.</abstract><cop>Amsterdam</cop><pub>Elsevier Ireland Ltd</pub><pmid>1892485</pmid><doi>10.1016/0021-9150(91)90080-M</doi><tpages>10</tpages></addata></record> |
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| ispartof | Atherosclerosis, 1991-06, Vol.88 (2), p.183-192 |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Animals Anticholesteremic Agents - pharmacology Benzylamines - pharmacology Bile - metabolism Bile acids Bile Acids and Salts - metabolism Biological and medical sciences Cholesterol Cholesterol - blood Cholesterol - metabolism Dog Dogs Ent. Stomatology Feces - chemistry Hypolipidemic drug Lipids - blood Lipoprotein Lipoproteins - blood Lovastatin - analogs & derivatives Lovastatin - pharmacology Male Medical sciences NB-598 Oxygenases - antagonists & inhibitors Pharmacology. Drug treatments Phospholipids - blood Simvastatin Squalene Squalene - blood Squalene - metabolism Squalene epoxidase inhibitor Squalene Monooxygenase Thiophenes - pharmacology Triglycerides - blood |
| title | Hypolipidemic effects of NB-598 in dogs |
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