| TVP1022 attenuates cardiac remodeling and kidney dysfunction in experimental volume overload-induced congestive heart failure. | |
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MedLine Citation:
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PMID: 21558446 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Despite the availability of many pharmacological and mechanical therapies, the mortality rate among patients with congestive heart failure (CHF) remains high. We tested the hypothesis that TVP1022 (the S-isomer of rasagiline; Azilect), a neuroprotective and cytoprotective molecule, is also cardioprotective in the settings of experimental CHF in rats. METHODS AND RESULTS: In rats with volume overload-induced CHF, we investigated the therapeutic efficacy of TVP1022 (7.5 mg/kg) on cardiac function, structure, biomarkers, and kidney function. Treatment with TVP1022 for 7 days before CHF induction prevented the increase in left ventricular end-diastolic area and end-systolic area, and the decrease in fractional shortening measured 14 days after CHF induction. Additionally, TVP1022 pretreatment attenuated CHF-induced cardiomyocyte hypertrophy, fibrosis, plasma and ventricular B-type natriuretic peptide levels, and reactive oxygen species expression. Further, in CHF rats, TVP1022 decreased cytochrome c and caspase 3 expression, thereby contributing to the cardioprotective efficacy of the drug. TVP1022 also enhanced the urinary Na(+) excretion and improved the glomerular filtration rate. Similar cardioprotective effects were obtained when TVP1022 was given to rats after CHF induction. CONCLUSIONS: TVP1022 attenuated the adverse functional, structural, and molecular alterations in CHF, rendering this drug a promising candidate for improving cardiac and renal function in this disease state. |
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Authors:
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Zaid A Abassi; Yaron D Barac; Sawa Kostin; Ariel Roguin; Elena Ovcharenko; Hoda Awad; Ayelet Blank; Orit Bar-Am; Tamar Amit; Jutta Schaper; Moussa Youdim; Ofer Binah |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2011-05-10 |
Journal Detail:
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Title: Circulation. Heart failure Volume: 4 ISSN: 1941-3297 ISO Abbreviation: Circ Heart Fail Publication Date: 2011 Jul |
Date Detail:
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Created Date: 2011-07-20 Completed Date: 2011-09-15 Revised Date: 2011-10-27 |
Medline Journal Info:
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Nlm Unique ID: 101479941 Medline TA: Circ Heart Fail Country: United States |
Other Details:
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Languages: eng Pagination: 463-73 Citation Subset: IM |
Affiliation:
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Department of Physiology, Rappaport Faculty of Medicine, Technion, Haifa, Israel. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cardiotonic Agents / pharmacology*, therapeutic use Caspase 3 / metabolism Cytochromes c / metabolism Disease Models, Animal Fibrosis / prevention & control Glomerular Filtration Rate / drug effects, physiology Heart Failure / drug therapy, metabolism, physiopathology* Hypertrophy / prevention & control Indans / pharmacology*, therapeutic use Kidney / drug effects*, physiopathology* Myocytes, Cardiac / pathology Natriuretic Peptide, Brain / metabolism Neuroprotective Agents / pharmacology*, therapeutic use Rats Rats, Sprague-Dawley Reactive Oxygen Species / metabolism Ventricular Remodeling / drug effects*, physiology |
| Chemical | |
Reg. No./Substance:
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0/Cardiotonic Agents; 0/Indans; 0/Neuroprotective Agents; 0/Reactive Oxygen Species; 114471-18-0/Natriuretic Peptide, Brain; 1875-50-9/rasagiline; 9007-43-6/Cytochromes c; EC 3.4.22.-/Caspase 3 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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