| d-Propranolol protects against oxidative stress and progressive cardiac dysfunction in iron overloaded rats. | |
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MedLine Citation:
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PMID: 22913465 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: JOURNAL ARTICLE Date: 2012-8-22 |
Journal Detail:
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Title: Canadian journal of physiology and pharmacology Volume: - ISSN: 1205-7541 ISO Abbreviation: Can. J. Physiol. Pharmacol. Publication Date: 2012 Aug |
Date Detail:
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Created Date: 2012-8-23 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0372712 Medline TA: Can J Physiol Pharmacol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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a Biochemistry & Molecular Biology, Division of Experimental Medicine, 4th Floor Ross Hall, The George Washington University Medical Center, 2300 Eye Street, N.W, Washington, DC 20037, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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