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Darapladib inhibits atherosclerosis development in type 2 diabetes mellitus Sprague-Dawley rat model
Increase in the low-density lipoprotein (LDL) level in diabetes mellitus and atherosclerosis is related to lipoprotein associated phospholipase A2 (Lp-PLA2). Lp-PLA2 is an enzyme that produces lysophosphatidylcholine (LysoPC) and oxidized nonesterified fatty acids (oxNEFA). LysoPC regulates inflamma...
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| Published in: | Endocrine regulations (Bratislava) 2018-04, Vol.52 (2), p.69-75 |
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| creator | Wihastuti, Titin Andri Heriansyah, Teuku Hanifa, Hanifa Andarini, Sri Sholichah, Zuhrotus Sulfia, Yuni Hendrati Adam, Aditya Angela Refialdinata, Jeki Lutfiana, Nurul Cholifah |
| description | Increase in the low-density lipoprotein (LDL) level in diabetes mellitus and atherosclerosis is related to lipoprotein associated phospholipase A2 (Lp-PLA2). Lp-PLA2 is an enzyme that produces lysophosphatidylcholine (LysoPC) and oxidized nonesterified fatty acids (oxNEFA). LysoPC regulates inflammation mediators, including intra-cellular adhesion molecule-1 (ICAM-1). Darapladib is known as a Lp-PLA2 specific inhibitor. The aim of this study was to reveal the effect of darapladib on the foam cell number, inducible nitric oxide synthase (iNOS), and ICAM-1 expression in aorta at early stages of the atherosclerosis in type 2 diabetes mellitus Sprague-Dawley rat model.
Thirty Sprague-Dawley male rats were divided into 3 main groups: control, rats with type 2 diabetes mellitus (T2DM), and T2DM rats treated with darapladib (T2DM-DP). Each group was divided into 2 subgroups according the time of treatment: 8-week and 16-week treatment group. Fasting blood glucose, insulin resistance, and lipid profile were measured and analyzed to ensure T2DM model. The foam cells number were detected using hematoxylin-eosin (HE) staining and the expression of iNOS and ICAM-1 was analyzed using double immunofluorescence staining.
Induction of T2DM in male Sprague-Dawley rats after high fat diet and streptozotocin injection was confirmed by elevated levels of total cholesterol and LDL and increased fasting glucose and insulin levels compared to controls after both times of treatment. Moreover, T2DM in rats induced a significant increase (p |
| doi_str_mv | 10.2478/enr-2018-0008 |
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Thirty Sprague-Dawley male rats were divided into 3 main groups: control, rats with type 2 diabetes mellitus (T2DM), and T2DM rats treated with darapladib (T2DM-DP). Each group was divided into 2 subgroups according the time of treatment: 8-week and 16-week treatment group. Fasting blood glucose, insulin resistance, and lipid profile were measured and analyzed to ensure T2DM model. The foam cells number were detected using hematoxylin-eosin (HE) staining and the expression of iNOS and ICAM-1 was analyzed using double immunofluorescence staining.
Induction of T2DM in male Sprague-Dawley rats after high fat diet and streptozotocin injection was confirmed by elevated levels of total cholesterol and LDL and increased fasting glucose and insulin levels compared to controls after both times of treatment. Moreover, T2DM in rats induced a significant increase (p<0.05) in the foam cells number and iNOS and ICAM-1 expression in aorta compared to controls after both treatment times. Darapladib treatment significantly reduced (p<0.05) foam cells number as well as iNOS expression in aorta in rats with T2DM after both treatment times. A significant decrease (p<0.05) in ICAM-1 expression in aorta was observed after darapladib treatment in rats with T2DM only after 8 weeks of treatment.
Our data indicate that darapladib can decrease the foam cells number, iNOS, and ICAM-1 expression in aorta at the early stages of atherosclerosis in T2DM rat model.</description><identifier>ISSN: 1210-0668</identifier><identifier>ISSN: 1336-0329</identifier><identifier>EISSN: 1336-0329</identifier><identifier>DOI: 10.2478/enr-2018-0008</identifier><identifier>PMID: 29715185</identifier><language>eng</language><publisher>Germany: De Gruyter Open</publisher><subject>Animals ; Aorta - drug effects ; Aorta - metabolism ; atherosclerosis ; Atherosclerosis - drug therapy ; Atherosclerosis - metabolism ; Benzaldehydes - administration & dosage ; Benzaldehydes - pharmacology ; darapladib ; Diabetes Mellitus, Experimental - drug therapy ; Diabetes Mellitus, Experimental - metabolism ; Diabetes Mellitus, Type 2 - drug therapy ; Diabetes Mellitus, Type 2 - metabolism ; Diet, High-Fat ; Oximes - administration & dosage ; Oximes - pharmacology ; Phospholipase A2 Inhibitors - administration & dosage ; Phospholipase A2 Inhibitors - pharmacology ; Rats ; Rats, Sprague-Dawley ; type 2 diabetes mellitus rat model</subject><ispartof>Endocrine regulations (Bratislava), 2018-04, Vol.52 (2), p.69-75</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3649-f3357e1859d71764d5441612b19288db10defc567ce195a4c9c042e89d2611453</citedby><cites>FETCH-LOGICAL-c3649-f3357e1859d71764d5441612b19288db10defc567ce195a4c9c042e89d2611453</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,864,2100,27922,27923</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29715185$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wihastuti, Titin Andri</creatorcontrib><creatorcontrib>Heriansyah, Teuku</creatorcontrib><creatorcontrib>Hanifa, Hanifa</creatorcontrib><creatorcontrib>Andarini, Sri</creatorcontrib><creatorcontrib>Sholichah, Zuhrotus</creatorcontrib><creatorcontrib>Sulfia, Yuni Hendrati</creatorcontrib><creatorcontrib>Adam, Aditya Angela</creatorcontrib><creatorcontrib>Refialdinata, Jeki</creatorcontrib><creatorcontrib>Lutfiana, Nurul Cholifah</creatorcontrib><title>Darapladib inhibits atherosclerosis development in type 2 diabetes mellitus Sprague-Dawley rat model</title><title>Endocrine regulations (Bratislava)</title><addtitle>Endocr Regul</addtitle><description>Increase in the low-density lipoprotein (LDL) level in diabetes mellitus and atherosclerosis is related to lipoprotein associated phospholipase A2 (Lp-PLA2). Lp-PLA2 is an enzyme that produces lysophosphatidylcholine (LysoPC) and oxidized nonesterified fatty acids (oxNEFA). LysoPC regulates inflammation mediators, including intra-cellular adhesion molecule-1 (ICAM-1). Darapladib is known as a Lp-PLA2 specific inhibitor. The aim of this study was to reveal the effect of darapladib on the foam cell number, inducible nitric oxide synthase (iNOS), and ICAM-1 expression in aorta at early stages of the atherosclerosis in type 2 diabetes mellitus Sprague-Dawley rat model.
Thirty Sprague-Dawley male rats were divided into 3 main groups: control, rats with type 2 diabetes mellitus (T2DM), and T2DM rats treated with darapladib (T2DM-DP). Each group was divided into 2 subgroups according the time of treatment: 8-week and 16-week treatment group. Fasting blood glucose, insulin resistance, and lipid profile were measured and analyzed to ensure T2DM model. The foam cells number were detected using hematoxylin-eosin (HE) staining and the expression of iNOS and ICAM-1 was analyzed using double immunofluorescence staining.
Induction of T2DM in male Sprague-Dawley rats after high fat diet and streptozotocin injection was confirmed by elevated levels of total cholesterol and LDL and increased fasting glucose and insulin levels compared to controls after both times of treatment. Moreover, T2DM in rats induced a significant increase (p<0.05) in the foam cells number and iNOS and ICAM-1 expression in aorta compared to controls after both treatment times. Darapladib treatment significantly reduced (p<0.05) foam cells number as well as iNOS expression in aorta in rats with T2DM after both treatment times. A significant decrease (p<0.05) in ICAM-1 expression in aorta was observed after darapladib treatment in rats with T2DM only after 8 weeks of treatment.
Our data indicate that darapladib can decrease the foam cells number, iNOS, and ICAM-1 expression in aorta at the early stages of atherosclerosis in T2DM rat model.</description><subject>Animals</subject><subject>Aorta - drug effects</subject><subject>Aorta - metabolism</subject><subject>atherosclerosis</subject><subject>Atherosclerosis - drug therapy</subject><subject>Atherosclerosis - metabolism</subject><subject>Benzaldehydes - administration & dosage</subject><subject>Benzaldehydes - pharmacology</subject><subject>darapladib</subject><subject>Diabetes Mellitus, Experimental - drug therapy</subject><subject>Diabetes Mellitus, Experimental - metabolism</subject><subject>Diabetes Mellitus, Type 2 - drug therapy</subject><subject>Diabetes Mellitus, Type 2 - metabolism</subject><subject>Diet, High-Fat</subject><subject>Oximes - administration & dosage</subject><subject>Oximes - pharmacology</subject><subject>Phospholipase A2 Inhibitors - administration & dosage</subject><subject>Phospholipase A2 Inhibitors - pharmacology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>type 2 diabetes mellitus rat model</subject><issn>1210-0668</issn><issn>1336-0329</issn><issn>1336-0329</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>DOA</sourceid><recordid>eNptkbtvFDEQxlcIREKgpEUuaTb4sX7RoQRCpEgUQG3N2rMXn_aF7SW6_x4fF1LRjEfWb755fE3zltFL3mnzAefUcspMSyk1z5pzJoRqqeD2ec05oy1Vypw1r3LeU8qNNOplc8atZpIZed6Ea0iwjhBiT-J8H_tYMoFyj2nJfjzGmEnA3zgu64RzqRAphxUJJyFCjwUzmXAcY9ky-b4m2G3YXsPDiAeSoJBpCTi-bl4MMGZ88_heND-_fP5x9bW9-3Zze_XprvVCdbYdhJAa61g2aKZVF2TXMcV4zyw3JvSMBhy8VNojsxI6bz3tOBobuGKsk-KiuT3phgX2bk1xgnRwC0T392NJOwepxLqXG4zyyiIbhtq6N8Z0kveAWltAi5RVrfcnrTUtvzbMxU0x-7opzLhs2XEqhNCillW0PaG-nisnHJ5aM-qOJrlqkjua5I4mVf7do_TWTxie6H-uVODjCXiAsWAKuEvboSZuv2xprhf8v7DkXFnxByDNn_4</recordid><startdate>20180401</startdate><enddate>20180401</enddate><creator>Wihastuti, Titin Andri</creator><creator>Heriansyah, Teuku</creator><creator>Hanifa, Hanifa</creator><creator>Andarini, Sri</creator><creator>Sholichah, Zuhrotus</creator><creator>Sulfia, Yuni Hendrati</creator><creator>Adam, Aditya Angela</creator><creator>Refialdinata, Jeki</creator><creator>Lutfiana, Nurul Cholifah</creator><general>De Gruyter Open</general><general>Sciendo</general><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><scope>DOA</scope></search><sort><creationdate>20180401</creationdate><title>Darapladib inhibits atherosclerosis development in type 2 diabetes mellitus Sprague-Dawley rat model</title><author>Wihastuti, Titin Andri ; Heriansyah, Teuku ; Hanifa, Hanifa ; Andarini, Sri ; Sholichah, Zuhrotus ; Sulfia, Yuni Hendrati ; Adam, Aditya Angela ; Refialdinata, Jeki ; Lutfiana, Nurul Cholifah</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3649-f3357e1859d71764d5441612b19288db10defc567ce195a4c9c042e89d2611453</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Animals</topic><topic>Aorta - drug effects</topic><topic>Aorta - metabolism</topic><topic>atherosclerosis</topic><topic>Atherosclerosis - drug therapy</topic><topic>Atherosclerosis - metabolism</topic><topic>Benzaldehydes - administration & dosage</topic><topic>Benzaldehydes - pharmacology</topic><topic>darapladib</topic><topic>Diabetes Mellitus, Experimental - drug therapy</topic><topic>Diabetes Mellitus, Experimental - metabolism</topic><topic>Diabetes Mellitus, Type 2 - drug therapy</topic><topic>Diabetes Mellitus, Type 2 - metabolism</topic><topic>Diet, High-Fat</topic><topic>Oximes - administration & dosage</topic><topic>Oximes - pharmacology</topic><topic>Phospholipase A2 Inhibitors - administration & dosage</topic><topic>Phospholipase A2 Inhibitors - pharmacology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>type 2 diabetes mellitus rat model</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wihastuti, Titin Andri</creatorcontrib><creatorcontrib>Heriansyah, Teuku</creatorcontrib><creatorcontrib>Hanifa, Hanifa</creatorcontrib><creatorcontrib>Andarini, Sri</creatorcontrib><creatorcontrib>Sholichah, Zuhrotus</creatorcontrib><creatorcontrib>Sulfia, Yuni Hendrati</creatorcontrib><creatorcontrib>Adam, Aditya Angela</creatorcontrib><creatorcontrib>Refialdinata, Jeki</creatorcontrib><creatorcontrib>Lutfiana, Nurul Cholifah</creatorcontrib><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><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Endocrine regulations (Bratislava)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wihastuti, Titin Andri</au><au>Heriansyah, Teuku</au><au>Hanifa, Hanifa</au><au>Andarini, Sri</au><au>Sholichah, Zuhrotus</au><au>Sulfia, Yuni Hendrati</au><au>Adam, Aditya Angela</au><au>Refialdinata, Jeki</au><au>Lutfiana, Nurul Cholifah</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Darapladib inhibits atherosclerosis development in type 2 diabetes mellitus Sprague-Dawley rat model</atitle><jtitle>Endocrine regulations (Bratislava)</jtitle><addtitle>Endocr Regul</addtitle><date>2018-04-01</date><risdate>2018</risdate><volume>52</volume><issue>2</issue><spage>69</spage><epage>75</epage><pages>69-75</pages><issn>1210-0668</issn><issn>1336-0329</issn><eissn>1336-0329</eissn><abstract>Increase in the low-density lipoprotein (LDL) level in diabetes mellitus and atherosclerosis is related to lipoprotein associated phospholipase A2 (Lp-PLA2). Lp-PLA2 is an enzyme that produces lysophosphatidylcholine (LysoPC) and oxidized nonesterified fatty acids (oxNEFA). LysoPC regulates inflammation mediators, including intra-cellular adhesion molecule-1 (ICAM-1). Darapladib is known as a Lp-PLA2 specific inhibitor. The aim of this study was to reveal the effect of darapladib on the foam cell number, inducible nitric oxide synthase (iNOS), and ICAM-1 expression in aorta at early stages of the atherosclerosis in type 2 diabetes mellitus Sprague-Dawley rat model.
Thirty Sprague-Dawley male rats were divided into 3 main groups: control, rats with type 2 diabetes mellitus (T2DM), and T2DM rats treated with darapladib (T2DM-DP). Each group was divided into 2 subgroups according the time of treatment: 8-week and 16-week treatment group. Fasting blood glucose, insulin resistance, and lipid profile were measured and analyzed to ensure T2DM model. The foam cells number were detected using hematoxylin-eosin (HE) staining and the expression of iNOS and ICAM-1 was analyzed using double immunofluorescence staining.
Induction of T2DM in male Sprague-Dawley rats after high fat diet and streptozotocin injection was confirmed by elevated levels of total cholesterol and LDL and increased fasting glucose and insulin levels compared to controls after both times of treatment. Moreover, T2DM in rats induced a significant increase (p<0.05) in the foam cells number and iNOS and ICAM-1 expression in aorta compared to controls after both treatment times. Darapladib treatment significantly reduced (p<0.05) foam cells number as well as iNOS expression in aorta in rats with T2DM after both treatment times. A significant decrease (p<0.05) in ICAM-1 expression in aorta was observed after darapladib treatment in rats with T2DM only after 8 weeks of treatment.
Our data indicate that darapladib can decrease the foam cells number, iNOS, and ICAM-1 expression in aorta at the early stages of atherosclerosis in T2DM rat model.</abstract><cop>Germany</cop><pub>De Gruyter Open</pub><pmid>29715185</pmid><doi>10.2478/enr-2018-0008</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Aorta - drug effects Aorta - metabolism atherosclerosis Atherosclerosis - drug therapy Atherosclerosis - metabolism Benzaldehydes - administration & dosage Benzaldehydes - pharmacology darapladib Diabetes Mellitus, Experimental - drug therapy Diabetes Mellitus, Experimental - metabolism Diabetes Mellitus, Type 2 - drug therapy Diabetes Mellitus, Type 2 - metabolism Diet, High-Fat Oximes - administration & dosage Oximes - pharmacology Phospholipase A2 Inhibitors - administration & dosage Phospholipase A2 Inhibitors - pharmacology Rats Rats, Sprague-Dawley type 2 diabetes mellitus rat model |
| title | Darapladib inhibits atherosclerosis development in type 2 diabetes mellitus Sprague-Dawley rat model |
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