Document Detail


d-Propranolol protects against oxidative stress and progressive cardiac dysfunction in iron overloaded rats.
MedLine Citation:
PMID:  22913465     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
d-Propranolol (d-Pro: 2-8 mg·(kg body mass)(-1)·day(-1)) protected against cardiac dysfunction and oxidative stress during 3-5 weeks of iron overload (2 mg Fe-dextran·(g body mass)(-1)·week(-1)) in Sprague-Dawley rats. At 3 weeks, hearts were perfused in working mode to obtain baseline function; red blood cell glutathione, plasma 8-isoprostane, neutrophil basal superoxide production, lysosomal-derived plasma N-acetyl-β-galactosaminidase (NAGA) activity, ventricular iron content, and cardiac iron deposition were assessed. Hearts from the Fe-treated group of rats exhibited lower cardiac work (26%) and output (CO, 24%); end-diastolic pressure rose 1.8-fold. Further, glutathione levels increased 2-fold, isoprostane levels increased 2.5-fold, neutrophil superoxide increased 3-fold, NAGA increased 4-fold, ventricular Fe increased 4.9-fold; and substantial atrial and ventricular Fe-deposition occurred. d-Pro (8 mg) restored heart function to the control levels, protected against oxidative stress, and decreased cardiac Fe levels. After 5 weeks of Fe treatment, echocardiography revealed that the following were depressed: percent fractional shortening (%FS, 31% lower); left ventricular (LV) ejection fraction (LVEF, 17%), CO (25%); and aortic pressure maximum (P(max), 24%). Mitral valve E/A declined by 18%, indicating diastolic dysfunction. Cardiac CD11b+ infiltrates were elevated. Low d-Pro (2 mg) provided modest protection, whereas 4-8 mg greatly improved LVEF (54%-75%), %FS (51%-81%), CO (43%-78%), P(max) (56%-100%), and E/A >100%; 8 mg decreased cardiac inflammation. Since d-Pro is an antioxidant and reduces cardiac Fe uptake as well as inflammation, these properties may preserve cardiac function during Fe overload.
Authors:
Jay H Kramer; Christopher F Spurney; Micaela Iantorno; Constantine Tziros; Joanna J Chmielinska; I Tong Mak; William B Weglicki
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2012-08-22
Journal Detail:
Title:  Canadian journal of physiology and pharmacology     Volume:  90     ISSN:  1205-7541     ISO Abbreviation:  Can. J. Physiol. Pharmacol.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-08-27     Completed Date:  2013-01-29     Revised Date:  2013-09-03    
Medline Journal Info:
Nlm Unique ID:  0372712     Medline TA:  Can J Physiol Pharmacol     Country:  Canada    
Other Details:
Languages:  eng     Pagination:  1257-68     Citation Subset:  IM    
Affiliation:
Biochemistry & Molecular Biology, Division of Experimental Medicine, The George Washington University Medical Center, Washington, DC 20037, USA. phyjhk@gwu.edu
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MeSH Terms
Descriptor/Qualifier:
Acetylglucosaminidase / blood
Adrenergic beta-Antagonists / administration & dosage,  chemistry,  therapeutic use*
Animals
Cardiac Output / drug effects
Disease Progression
Dose-Response Relationship, Drug
Echocardiography
Erythrocytes / drug effects,  metabolism
Glutathione
Heart Diseases / blood,  etiology,  metabolism,  prevention & control*
Iron Overload / blood,  complications,  drug therapy*,  metabolism
Male
Myocardium / metabolism
Neutrophils / drug effects,  enzymology
Oxidative Stress / drug effects*
Perfusion
Propranolol / administration & dosage,  chemistry,  therapeutic use*
Rats
Rats, Sprague-Dawley
Stereoisomerism
Superoxide Dismutase / metabolism
Treatment Outcome
Grant Support
ID/Acronym/Agency:
R01 HL066226/HL/NHLBI NIH HHS; R01-HL66226/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Adrenergic beta-Antagonists; 525-66-6/Propranolol; 70-18-8/Glutathione; EC 1.15.1.1/Superoxide Dismutase; EC 3.2.1.52/Acetylglucosaminidase
Comments/Corrections

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