| A therapeutic approach to treat cardiovascular dysfunction of diabetes. | |
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MedLine Citation:
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PMID: 21474293 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Diabetes greatly increases risk of cardiovascular dysfunction and interruptions of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) have been shown to reduce the risk by alteration in extracellular matrix. We hypothesized that minocycline induced MMP-2 and MMP-9 inhibition can be enhanced by aspirin (through its COX and tPA inhibitory action) and this combination can reduce cardiovascular dysfunction of diabetes. Four weeks after diabetes induction (streptozotocin, 55mg/kg, i.p.), rats were treated with minocycline (50mg/kg, p.o.), aspirin (50mg/kg, p.o.), or minocycline (50mg/kg, p.o.) plus aspirin (50mg/kg, p.o.) for a period of next four weeks. At the end of eighth week arterial pressure, heart rate and left ventricular pressure were recorded. Contractile response to phenylephrine (10(-5)M) and relaxation responses to acetylcholine (10(-9)-10(-4)M) were obtained from aortic rings of diabetic rats. Gel zymography was performed to evaluate MMP-2 and MMP-9 levels. Heart rate, mean arterial pressure, dp/dt(max) and dp/dt(min) were found significantly decreased in STZ diabetic rats when compared with normoglycemic group. Treatment with combination of minocycline and aspirin significantly ameliorate these compared to vehicle treated diabetic group. Endothelium-dependent relaxation responses induced by acetylcholine were decreased in diabetic rats and significantly higher in combination treated group. Collagen, MMP-2 and MMP-9 levels were significantly decreased in combined treated group when compared with diabetic control. Present study revealed that aspirin potentate minocycline induced MMP-2 and MMP-9 inhibition to ameliorate cardiovascular dysfunction of diabetes and this combination can be an approach for the treatment. |
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Authors:
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L K Bhatt; A Veeranjaneyulu |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-4-5 |
Journal Detail:
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Title: Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie Volume: - ISSN: 1618-1433 ISO Abbreviation: - Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-4-8 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9208920 Medline TA: Exp Toxicol Pathol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 Elsevier GmbH. All rights reserved. |
Affiliation:
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Department of Pharmacology, School of Pharmacy and Technology Management, NMIMS University, Vile Parle (W), Mumbai, Maharashtra 400 056, India. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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