Document Detail


Resorcylidene aminoguanidine induces antithrombotic action that is not dependent on its antiglycation activity.
MedLine Citation:
PMID:  19635586     Owner:  NLM     Status:  In-Process    
Abstract/OtherAbstract:
There is good evidence supporting the notion that aminoguanidine(AG)-derived compounds prevent glycation/glycooxidation-dependent processes and therefore inhibit late diabetic complications. The aim of the present work was to analyse the antithrombotic action and antiglycation activity of beta-resorcylidene aminoguanidine (RAG) in comparison with another commonly used aminoguanidine (AG)-derived compound, pyridoxal aminoguanidine (PAG). In vitro RAG and PAG prevented exhaustive glycation and glycooxidation of BSA to a similar extent. However, merely RAG showed almost complete binding to sepharose-immobilized heparin, while PAG and other AG derivatives had much poorer affinities. In the model of in vivo thrombosis in Wistar rats with extracorporeal circulation RAG (i.v. 30 mg/kg), but not PAG, produced sustained (2 h) antithrombotic effect, which was abrogated by indomethacin (5 mg/kg) and rofecoxib (1 mg/kg). The 60-day treatment of streptozotocin-diabetic animals with RAG (p.o. 4 mg/kg) significantly decreased plasma concentration of a thromboxane B(2) and reduced whole blood platelet aggregability triggered by ADP or collagen. In conclusion, although RAG and PAG displayed similar antiglycation and antioxidation activities in vitro, only RAG showed antithrombotic activity in vivo that involved activation of COX-2/PGI(2) pathway. Our results indicate that designing novel RAG derivatives with optimal antithrombotic and antiglycation activities may prove useful to treat diabetic complications.
Authors:
Cezary Watala; Marcin Dobaczewski; Piotr Kazmierczak; Jerzy Gebicki; Marek Nocun; Ingrid Zitnanova; Olga Ulicna; Zdena Durackova; Iveta Waczulíková; Jozef Carsky; Stefan Chlopicki
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-07-24
Journal Detail:
Title:  Vascular pharmacology     Volume:  51     ISSN:  1879-3649     ISO Abbreviation:  Vascul. Pharmacol.     Publication Date:  2009 Oct 
Date Detail:
Created Date:  2009-10-19     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101130615     Medline TA:  Vascul Pharmacol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  275-83     Citation Subset:  IM    
Affiliation:
Department of Haemostasis and Haemostatic Disorders, Chair of Laboratory Diagnostics, Medical University of Lodz, University Hospital no. 2, Lodz, Poland. cwatala@csk.umed.lodz.pl
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