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Cardiovascular effects induced by Polymeric 3-alkylpyridinium salts from the marine sponge Reniera sarai Δ
MedLine Citation:
PMID:  22846421     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Water-soluble polymeric 3-alkylpyridinum salts (poly-APS), isolated from the marine sponge Reniera sarai, are natural products with promising biomedical applications. However, their ability to form nonspecific cell membrane pores raises safety issues. Therefore, the aim of the present study was to investigate the direct toxic effects of poly-APS on the cardiovascular system. To study the impact of poly-APS toxicodynamics on vascular function, the relaxation and contraction responses of isolated rat thoracic aortas incubated in poly-APS solutions (0.01-10 μM) were tested. In addition, cardiac toxicity was studied by measuring coronary flow, lactate dehydrogenase release rate, left ventricular pressure, heart rate, and the duration of arrhythmias in isolated rat hearts perfused with poly-APS (0.001-1 μM). Poly-APS diminished endothelium-dependent relaxation and contraction in a concentration- and time-dependent manner. Endothelial function was affected earlier and to a greater extent than contractile responses. Likewise, in isolated hearts the most evident cardiotoxic effects were observed after perfusion with the highest concentration (1 μM) of poly-APS: compared to the control group the coronary flow and heart rate were diminished by 2.2- and 1.8-fold, while lactate dehydrogenase release rate and left ventricular pressure were increased by 7.8- and 2.2-fold (all P<0.001). Further, poly-APS had evident proarrhythmogenic activity in a concentration-dependent manner. However, in the low concentration range (1-10 nM) poly-APS showed only minor toxicity. Our results confirmed the direct toxic effects of poly-APS on the rat cardiovascular system. Therefore, it seems reasonable to conclude that the use of poly-APS as therapeutic adjuvants has limited safety margins.
Authors:
Mojca Lunder; Gorazd Drevenšek; Simon Hawlina; Kristina Sepčić; Lovro Ziberna
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-27
Journal Detail:
Title:  Toxicon : official journal of the International Society on Toxinology     Volume:  -     ISSN:  1879-3150     ISO Abbreviation:  -     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-7-31     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1307333     Medline TA:  Toxicon     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier Ltd.
Affiliation:
Institute of Pharmacology and Experimental Toxicology, Faculty of Medicine, University of Ljubljana, Korytkova 2, 1000 Ljubljana, Slovenia; Barsos Medical Centre, Gregorčičeva 7, 1000 Ljubljana, Slovenia.
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