3',4'-Dihydroxyflavonol antioxidant attenuates diastolic dysfunction and cardiac remodeling in streptozotocin-induced diabetic m(Ren2)27 rats.

<h4>Background</h4>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 l...

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Autores principales:	Fay Lin Khong, Yuan Zhang, Amanda J Edgley, Weier Qi, Kim A Connelly, Owen L Woodman, Henry Krum, Darren J Kelly
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b3c3d1f9a0624ba1b05fbec78e20252e
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spelling	oai:doaj.org-article:b3c3d1f9a0624ba1b05fbec78e20252e2021-11-18T06:49:08Z3',4'-Dihydroxyflavonol antioxidant attenuates diastolic dysfunction and cardiac remodeling in streptozotocin-induced diabetic m(Ren2)27 rats.1932-620310.1371/journal.pone.0022777https://doaj.org/article/b3c3d1f9a0624ba1b05fbec78e20252e2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21829510/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions</h4>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.Fay Lin KhongYuan ZhangAmanda J EdgleyWeier QiKim A ConnellyOwen L WoodmanHenry KrumDarren J KellyPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 7, p e22777 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Fay Lin Khong Yuan Zhang Amanda J Edgley Weier Qi Kim A Connelly Owen L Woodman Henry Krum Darren J Kelly 3',4'-Dihydroxyflavonol antioxidant attenuates diastolic dysfunction and cardiac remodeling in streptozotocin-induced diabetic m(Ren2)27 rats.
description	<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions</h4>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.
format	article
author	Fay Lin Khong Yuan Zhang Amanda J Edgley Weier Qi Kim A Connelly Owen L Woodman Henry Krum Darren J Kelly
author_facet	Fay Lin Khong Yuan Zhang Amanda J Edgley Weier Qi Kim A Connelly Owen L Woodman Henry Krum Darren J Kelly
author_sort	Fay Lin Khong
title	3',4'-Dihydroxyflavonol antioxidant attenuates diastolic dysfunction and cardiac remodeling in streptozotocin-induced diabetic m(Ren2)27 rats.
title_short	3',4'-Dihydroxyflavonol antioxidant attenuates diastolic dysfunction and cardiac remodeling in streptozotocin-induced diabetic m(Ren2)27 rats.
title_full	3',4'-Dihydroxyflavonol antioxidant attenuates diastolic dysfunction and cardiac remodeling in streptozotocin-induced diabetic m(Ren2)27 rats.
title_fullStr	3',4'-Dihydroxyflavonol antioxidant attenuates diastolic dysfunction and cardiac remodeling in streptozotocin-induced diabetic m(Ren2)27 rats.
title_full_unstemmed	3',4'-Dihydroxyflavonol antioxidant attenuates diastolic dysfunction and cardiac remodeling in streptozotocin-induced diabetic m(Ren2)27 rats.
title_sort	3',4'-dihydroxyflavonol antioxidant attenuates diastolic dysfunction and cardiac remodeling in streptozotocin-induced diabetic m(ren2)27 rats.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/b3c3d1f9a0624ba1b05fbec78e20252e
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3',4'-Dihydroxyflavonol antioxidant attenuates diastolic dysfunction and cardiac remodeling in streptozotocin-induced diabetic m(Ren2)27 rats.

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