title: 3',4'-Dihydroxyflavonol antioxidant attenuates diastolic dysfunction and cardiac remodeling in streptozotocin-induced diabetic m(Ren2)27 rats.
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.
  
  
  RESULTS
  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.
authors.affiliation: Department of Medicine, The University of Melbourne, St Vincent's Hospital Fitzroy, Melbourne, Victoria, Australia.
authors.forename: Fay Lin
authors.initials: FL
authors.lastname: Khong
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Edgley
authors.forename: Weier
authors.initials: W
authors.lastname: Qi
authors.forename: Kim A
authors.initials: KA
authors.lastname: Connelly
authors.forename: Owen L
authors.initials: OL
authors.lastname: Woodman
authors.forename: Henry
authors.initials: H
authors.lastname: Krum
authors.forename: Darren J
authors.initials: DJ
authors.lastname: Kelly
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001345:Autoradiography; D006328:Cardiac Catheterization; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D058065:Diabetic Cardiomyopathies / Q000188:drug therapy*; D004452:Echocardiography; D044948:Flavonols / Q000627:therapeutic use*; D006720:Homozygote; D017403:In Situ Hybridization; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D055647:Rats, Transgenic; D017382:Reactive Oxygen Species / Q000378:metabolism*; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy*
chemical_list: D000975:Antioxidants; D044948:Flavonols; D017382:Reactive Oxygen Species; D019255:NADPH Oxidases; C529890:3',4'-dihydroxyflavonol