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3',4'-Dihydroxyflavonol Antioxidant Attenuates Diastolic Dysfunction and Cardiac Remodeling in Streptozotocin-Induced Diabetic m
Diabetic cardiomyopathy (DCM) is an increasingly recognized cause of chronic heart failure amongst diabetic patients. Both increased reactive oxygen species (ROS) generation and impaired ROS scavenging have been implicated in the pathogenesis of hyperglycemia-induced left ventricular dysfunction, ca...
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Published in: | PloS one 2011-07, Vol.6 (7), p.e22777 |
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creator | Khong, Fay Lin Zhang, Yuan Edgley, Amanda J Qi, Weier Connelly, Kim A Woodman, Owen L Krum, Henry Kelly, Darren J |
description | Diabetic cardiomyopathy (DCM) is an increasingly recognized cause of chronic heart failure amongst diabetic patients. Both increased reactive oxygen species (ROS) generation and impaired ROS scavenging have been implicated in the pathogenesis of hyperglycemia-induced left ventricular dysfunction, cardiac fibrosis, apoptosis and hypertrophy. We hypothesized that 3',4'-dihydroxyflavonol (DiOHF), a small highly lipid soluble synthetic flavonol, may prevent DCM by scavenging ROS, thus preventing ROS-induced cardiac damage. Six week old homozygous Ren-2 rats were randomized to receive either streptozotocin or citrate buffer, then further randomized to receive either DiOHF (1 mg/kg/day) by oral gavage or vehicle for six weeks. Cardiac function was assessed via echocardiography and left ventricular cardiac catheterization before the animals were sacrificed and hearts removed for histological and molecular analyses. Diabetic Ren-2 rats showed evidence of diastolic dysfunction with prolonged deceleration time, reduced E/A ratio, and increased slope of end-diastolic pressure volume relationship (EDPVR) in association with marked interstitial fibrosis and oxidative stress (all P |
doi_str_mv | 10.1371/journal.pone.0022777 |
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Both increased reactive oxygen species (ROS) generation and impaired ROS scavenging have been implicated in the pathogenesis of hyperglycemia-induced left ventricular dysfunction, cardiac fibrosis, apoptosis and hypertrophy. We hypothesized that 3',4'-dihydroxyflavonol (DiOHF), a small highly lipid soluble synthetic flavonol, may prevent DCM by scavenging ROS, thus preventing ROS-induced cardiac damage. Six week old homozygous Ren-2 rats were randomized to receive either streptozotocin or citrate buffer, then further randomized to receive either DiOHF (1 mg/kg/day) by oral gavage or vehicle for six weeks. Cardiac function was assessed via echocardiography and left ventricular cardiac catheterization before the animals were sacrificed and hearts removed for histological and molecular analyses. Diabetic Ren-2 rats showed evidence of diastolic dysfunction with prolonged deceleration time, reduced E/A ratio, and increased slope of end-diastolic pressure volume relationship (EDPVR) in association with marked interstitial fibrosis and oxidative stress (all P<0.05 vs control Ren-2). Treatment with DiOHF prevented the development of diastolic dysfunction and was associated with reduced oxidative stress and interstitial fibrosis (all P<0.05 vs untreated diabetic Ren-2 rats). In contrast, few changes were seen in non-diabetic treated animals compared to untreated counterparts. Inhibition of ROS production and action by DiOHF improved diastolic function and reduced myocyte hypertrophy as well as collagen deposition. These findings suggest the potential clinical utility of antioxidative compounds such as flavonols in the prevention of diabetes-associated cardiac dysfunction.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0022777</identifier><language>eng</language><publisher>Public Library of Science</publisher><subject>Antioxidants (Nutrients) ; Apoptosis ; Collagen ; Flavonoids ; Heart ; Heart failure ; Hyperglycemia ; Streptozocin</subject><ispartof>PloS one, 2011-07, Vol.6 (7), p.e22777</ispartof><rights>COPYRIGHT 2011 Public Library of Science</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids></links><search><creatorcontrib>Khong, Fay Lin</creatorcontrib><creatorcontrib>Zhang, Yuan</creatorcontrib><creatorcontrib>Edgley, Amanda J</creatorcontrib><creatorcontrib>Qi, Weier</creatorcontrib><creatorcontrib>Connelly, Kim A</creatorcontrib><creatorcontrib>Woodman, Owen L</creatorcontrib><creatorcontrib>Krum, Henry</creatorcontrib><creatorcontrib>Kelly, Darren J</creatorcontrib><title>3',4'-Dihydroxyflavonol Antioxidant Attenuates Diastolic Dysfunction and Cardiac Remodeling in Streptozotocin-Induced Diabetic m</title><title>PloS one</title><description>Diabetic cardiomyopathy (DCM) is an increasingly recognized cause of chronic heart failure amongst diabetic patients. Both increased reactive oxygen species (ROS) generation and impaired ROS scavenging have been implicated in the pathogenesis of hyperglycemia-induced left ventricular dysfunction, cardiac fibrosis, apoptosis and hypertrophy. We hypothesized that 3',4'-dihydroxyflavonol (DiOHF), a small highly lipid soluble synthetic flavonol, may prevent DCM by scavenging ROS, thus preventing ROS-induced cardiac damage. Six week old homozygous Ren-2 rats were randomized to receive either streptozotocin or citrate buffer, then further randomized to receive either DiOHF (1 mg/kg/day) by oral gavage or vehicle for six weeks. Cardiac function was assessed via echocardiography and left ventricular cardiac catheterization before the animals were sacrificed and hearts removed for histological and molecular analyses. Diabetic Ren-2 rats showed evidence of diastolic dysfunction with prolonged deceleration time, reduced E/A ratio, and increased slope of end-diastolic pressure volume relationship (EDPVR) in association with marked interstitial fibrosis and oxidative stress (all P<0.05 vs control Ren-2). Treatment with DiOHF prevented the development of diastolic dysfunction and was associated with reduced oxidative stress and interstitial fibrosis (all P<0.05 vs untreated diabetic Ren-2 rats). In contrast, few changes were seen in non-diabetic treated animals compared to untreated counterparts. Inhibition of ROS production and action by DiOHF improved diastolic function and reduced myocyte hypertrophy as well as collagen deposition. These findings suggest the potential clinical utility of antioxidative compounds such as flavonols in the prevention of diabetes-associated cardiac dysfunction.</description><subject>Antioxidants (Nutrients)</subject><subject>Apoptosis</subject><subject>Collagen</subject><subject>Flavonoids</subject><subject>Heart</subject><subject>Heart failure</subject><subject>Hyperglycemia</subject><subject>Streptozocin</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><recordid>eNqF0E9PwjAYx_HFaCKi78BDTxITh-26tdtxAf-QmJAA8Uqere0oKS1ZOwOefOlC9IAnT89z-OR7-EXRLcFDQjl5XLuutWCGW2flEOMk4ZyfRT1S0CRmCabnJ_9ldOX9GuOM5oz1oi86eEgH8Viv9qJ1u70y8OGsM6i0QbudFmADKkOQtoMgPRpr8MEZXaPx3qvO1gdlEViBRtAKDTWayY0T0mjbIG3RPLRyG9ynC67WNp5Y0dVSHDOVDIfK5jq6UGC8vPm9_Wjx_LQYvcZv05fJqHyLm6LgsapklXMsqjRVJCMqzyguGCaKKUY4z1JG0jxPqrSqaC0SBQzyTAFUFChLIKP96P4n24CRS21rZ4PchQY675eT-WxZppzlOT0s94-dvv-1dyd2JcGElXemO87iT-E3zK6CUA</recordid><startdate>20110728</startdate><enddate>20110728</enddate><creator>Khong, Fay Lin</creator><creator>Zhang, Yuan</creator><creator>Edgley, Amanda J</creator><creator>Qi, Weier</creator><creator>Connelly, Kim A</creator><creator>Woodman, Owen L</creator><creator>Krum, Henry</creator><creator>Kelly, Darren J</creator><general>Public Library of Science</general><scope>IOV</scope><scope>ISR</scope></search><sort><creationdate>20110728</creationdate><title>3',4'-Dihydroxyflavonol Antioxidant Attenuates Diastolic Dysfunction and Cardiac Remodeling in Streptozotocin-Induced Diabetic m</title><author>Khong, Fay Lin ; Zhang, Yuan ; Edgley, Amanda J ; Qi, Weier ; Connelly, Kim A ; Woodman, Owen L ; Krum, Henry ; Kelly, Darren J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-g997-fbeb870db44f151f85309601f6f617754614882b4bb3cd2fa6a85faab3a362a53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Antioxidants (Nutrients)</topic><topic>Apoptosis</topic><topic>Collagen</topic><topic>Flavonoids</topic><topic>Heart</topic><topic>Heart failure</topic><topic>Hyperglycemia</topic><topic>Streptozocin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Khong, Fay Lin</creatorcontrib><creatorcontrib>Zhang, Yuan</creatorcontrib><creatorcontrib>Edgley, Amanda J</creatorcontrib><creatorcontrib>Qi, Weier</creatorcontrib><creatorcontrib>Connelly, Kim A</creatorcontrib><creatorcontrib>Woodman, Owen L</creatorcontrib><creatorcontrib>Krum, Henry</creatorcontrib><creatorcontrib>Kelly, Darren J</creatorcontrib><collection>Opposing Viewpoints Resource Center</collection><collection>Science in Context</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Khong, Fay Lin</au><au>Zhang, Yuan</au><au>Edgley, Amanda J</au><au>Qi, Weier</au><au>Connelly, Kim A</au><au>Woodman, Owen L</au><au>Krum, Henry</au><au>Kelly, Darren J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>3',4'-Dihydroxyflavonol Antioxidant Attenuates Diastolic Dysfunction and Cardiac Remodeling in Streptozotocin-Induced Diabetic m</atitle><jtitle>PloS one</jtitle><date>2011-07-28</date><risdate>2011</risdate><volume>6</volume><issue>7</issue><spage>e22777</spage><pages>e22777-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Diabetic cardiomyopathy (DCM) is an increasingly recognized cause of chronic heart failure amongst diabetic patients. Both increased reactive oxygen species (ROS) generation and impaired ROS scavenging have been implicated in the pathogenesis of hyperglycemia-induced left ventricular dysfunction, cardiac fibrosis, apoptosis and hypertrophy. We hypothesized that 3',4'-dihydroxyflavonol (DiOHF), a small highly lipid soluble synthetic flavonol, may prevent DCM by scavenging ROS, thus preventing ROS-induced cardiac damage. Six week old homozygous Ren-2 rats were randomized to receive either streptozotocin or citrate buffer, then further randomized to receive either DiOHF (1 mg/kg/day) by oral gavage or vehicle for six weeks. Cardiac function was assessed via echocardiography and left ventricular cardiac catheterization before the animals were sacrificed and hearts removed for histological and molecular analyses. Diabetic Ren-2 rats showed evidence of diastolic dysfunction with prolonged deceleration time, reduced E/A ratio, and increased slope of end-diastolic pressure volume relationship (EDPVR) in association with marked interstitial fibrosis and oxidative stress (all P<0.05 vs control Ren-2). Treatment with DiOHF prevented the development of diastolic dysfunction and was associated with reduced oxidative stress and interstitial fibrosis (all P<0.05 vs untreated diabetic Ren-2 rats). In contrast, few changes were seen in non-diabetic treated animals compared to untreated counterparts. Inhibition of ROS production and action by DiOHF improved diastolic function and reduced myocyte hypertrophy as well as collagen deposition. These findings suggest the potential clinical utility of antioxidative compounds such as flavonols in the prevention of diabetes-associated cardiac dysfunction.</abstract><pub>Public Library of Science</pub><doi>10.1371/journal.pone.0022777</doi><tpages>e22777</tpages></addata></record> |
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subjects | Antioxidants (Nutrients) Apoptosis Collagen Flavonoids Heart Heart failure Hyperglycemia Streptozocin |
title | 3',4'-Dihydroxyflavonol Antioxidant Attenuates Diastolic Dysfunction and Cardiac Remodeling in Streptozotocin-Induced Diabetic m |
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