Τόμος 10 (1996) – Τεύχος 2 – Άρθρο 3 – Επιθεώρηση Κλινικής Φαρμακολογίας και Φαρμακοκινητικής-Διεθνής Έκδοση – Volume 10 (1996) – Issue 2 – Article 3 – Epitheorese Klinikes Farmakologias και Farmakokinetikes-International Edition

Title Implication of free radicals for platelet aggregation: antiplatelet effects of free radical scavengers, ex vivo
Authors Spiros Karkabounas, Georgios Sofis and Angelos Evangelou

Laboratory of Experimental Physiology, Faculty of Medicine, University of Ioannina, 45110 Ioannina, Greece

Citation Karkabounas, S., Sofis, G., Evangelou, A.: Implication of free radicals for platelet aggregation; antiplatelet effects of free radical scavengers, ex vivo, Epitheorese Klin. Farmakol. Farmakokinet. 10(2): 84-91 (1996)
Publication Date Received for publication: 1 April 1996

Accepted for publication: 10 June 1996

Full Text Language English
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Keywords Free radicals, platelet aggregation, antiplatelet effects, free radical scavengers, antioxidants, PAF, arachidonic acid, vitamin C, reduced glutathione, butyl hydroxytoluene, trimetazidine, phenylbutylnitrone, dehydroascorbic acid, ex vivo.
Other Terms review article
Summary The possible implication of free radicals for the biochemical procedures leading to platelet aggregation and its inhibition was investigated by means of weil known free radical scavengers and/or antioxidants. Washed rabbit platelets were used in order to investigate the possible effects of free radical scavengers and/or antioxidants, on PAF- and AA-induced platelet aggregation. Platelet suspensions were incubated with CP/CPK prior to the aggregation tests. Pretreatment of platelets with ASA was applied for testing PAF-induced aggregation. Vitamin C, reduced glutathione (GSH), butyl hydroxytoluene (BHT), trimetazidine (TMZ), phenylbutylnitrone (PBN) and the oxidized form of ascorbic acid, dehydroascorbic acid (DHAA), were added in platelet suspensions in various concentrations before aggregation with PAF and AA. Vitamin C oxidation during platelet activation with PAF was photometrically monitored. Effects of the substances tested, on linoleic acid-lipoxygenase reaction was also elaborated, in vitro. All substances tested, except DHAA, inhibited PAF- and AA-induced irreversible platelet aggregation at final concentrations of 10-4 M (IC50) and 10-3 M (IC100). Linoleic acid-lipoxygenase reaction was also remarkably inhibited by concentrations of 10-5 M, of all of the substances tested, except of DHAA. Inhibition of PAF- and AA-induced platelet aggregation and linoleic acid-lipoxygenase reaction by well-known free radical scavengers and/or antioxidants, oxidation of vit. C during platelet activation and failure of dehydroascorbic acid to exert any inhibiting effect on the above procedures, indicate that intraplatelet free radicals are possibly involved in platelet aggregation. Scavenging of such free radical species or reducing effects of the substances tested may prevent oxidation of Fe2+ to Fe3+ at the active sites of the enzymes involved to arachidonic acid metabolism (lipo- and cyclooxygenase), inducing thus inactivation of the biochemical pathways leading to platelet aggregation.
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