title: Resorcylidene aminoguanidine induces antithrombotic action that is not dependent on its antiglycation activity.
abstract: 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.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
authors.forename: Cezary
authors.initials: C
authors.lastname: Watala
authors.forename: Marcin
authors.initials: M
authors.lastname: Dobaczewski
authors.forename: Piotr
authors.initials: P
authors.lastname: Kazmierczak
authors.forename: Jerzy
authors.initials: J
authors.lastname: Gebicki
authors.forename: Marek
authors.initials: M
authors.lastname: Nocun
authors.forename: Ingrid
authors.initials: I
authors.lastname: Zitnanova
authors.forename: Olga
authors.initials: O
authors.lastname: Ulicna
authors.forename: Zdena
authors.initials: Z
authors.lastname: Durackova
authors.forename: Iveta
authors.initials: I
authors.lastname: Waczulíková
authors.forename: Jozef
authors.initials: J
authors.lastname: Carsky
authors.forename: Stefan
authors.initials: S
authors.lastname: Chlopicki
mesh_terms: D000818:Animals; D002417:Cattle; D005343:Fibrinolytic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D006031:Glycosylation / Q000187:drug effects; D006146:Guanidines / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012710:Serum Albumin, Bovine / Q000378:metabolism; D013927:Thrombosis / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D005343:Fibrinolytic Agents; D017127:Glycation End Products, Advanced; D006146:Guanidines; C115168:resorcylidene aminoguanidine; D012710:Serum Albumin, Bovine