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

Khong, F, Zhang, Y, Edgley, A, Qi, W, Connelly, K, Woodman, O, Krum, H and Kelly, D 2011, '3',4'-Dihydroxyflavonol antioxidant attenuates aiastolic dysfunction and cardiac remodeling in streptozotocin-induced diabetic m(Ren2)27 rats', Plos one, vol. 6, no. 7, pp. 1-14.


Document type: Journal Article
Collection: Journal Articles

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Title 3',4'-Dihydroxyflavonol antioxidant attenuates aiastolic dysfunction and cardiac remodeling in streptozotocin-induced diabetic m(Ren2)27 rats
Author(s) Khong, F
Zhang, Y
Edgley, A
Qi, W
Connelly, K
Woodman, O
Krum, H
Kelly, D
Year 2011
Journal name Plos one
Volume number 6
Issue number 7
Start page 1
End page 14
Total pages 14
Publisher Public Library of Science
Abstract Background 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. Methodology/Principal Findings 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. Conclusions 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.
Subject Cardiology (incl. Cardiovascular Diseases)
Keyword(s) 3'
4' dihydroxyflavonol
flavonol derivative
unclassified drug
animal experiment
animal model
animal tissue
antioxidant activity
article
controlled study
diabetes mellitus
diastolic dysfunction
drug effect
heart catheterization
heart function
heart left ventricle enddiastolic pressure
heart left ventricle enddiastolic volume
heart muscle fibrosis
heart protection
heart ventricle remodeling
male
nonhuman
nucleotide sequence
oxidative stress
primary prevention
rat
streptozocin diabetes
DOI - identifier 10.1371/journal.pone.0022777
Copyright notice © 2011 Khong et al.
ISSN 1932-6203
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