Antiplatelet effect of catechol is related to inhibition of cyclooxygenase, reactive oxygen species, ERK/p38 signaling and thromboxane A2 production
Journal
PLoS ONE
Journal Volume
9
Journal Issue
8
Date Issued
2014
Author(s)
Chang M.-C.
Chan C.-P.
Yeung S.-Y.
Yeh C.-Y.
Cheng R.-H.
Abstract
Catechol (benzenediol) is present in plant-derived products, such as vegetables, fruits, coffee, tea, wine, areca nut and cigarette smoke. Because platelet dysfunction is a risk factor of cardiovascular diseases, including stroke, atherosclerosis and myocardial infarction, the purpose of this study was to evaluate the anti-platelet and anti-inflammatory effect of catechol and its mechanisms. The effects of catechol on cyclooxygenase (COX) activity, arachidonic acid (AA)-induced aggregation, thromboxane B2 (TXB 2) production, lactate dehydrogenase (LDH) release, reactive oxygen species (ROS) production and extracellular signal-regulated kinase (ERK)/p38 phosphorylation were determined in rabbit platelets. In addition, its effect on IL-1β-induced prostaglandin E2 (PGE2) production by fibroblasts was determined. The ex vivo effect of catechol on platelet aggregation was also measured. Catechol (5-25 μM) suppressed AA-induced platelet aggregation and inhibited TXB2 production at concentrations of 0.5-5 μM; however, it showed little cytotoxicity and did not alter U46619-induced platelet aggregation. Catechol (10-50 μM) suppressed COX-1 activity by 29-44% and COX-2 activity by 29-50%. It also inhibited IL-1β-induced PGE2 production, but not COX-2 expression of fibroblasts. Moreover, catechol (1-10 μM) attenuated AA-induced ROS production in platelets and phorbol myristate acetate (PMA)-induced ROS production in human polymorphonuclear leukocytes. Exposure of platelets to catechol decreased AA-induced ERK and p38 phosphorylation. Finally, intravenous administration of catechol (2.5-5 μmole/mouse) attenuated ex vivo AA-induced platelet aggregation. These results suggest that catechol exhibited anti-platelet and anti-inflammatory effects, which were mediated by inhibition of COX, ROS and TXA2 production as well as ERK/p38 phosphorylation. The anti-platelet effect of catechol was confirmed by ex vivo analysis. Exposure to catechol may affect platelet function and thus cardiovascular health. ? 2014 Chang et al.
SDGs
Other Subjects
15 hydroxy 11alpha,9alpha epoxymethanoprosta 5,13 dienoic acid; antithrombocytic agent; arachidonic acid; catechol; catechol derivative; mitogen activated protein kinase p38; prostaglandin synthase; prostaglandin synthase inhibitor; reactive oxygen metabolite; thromboxane A2; animal; antagonists and inhibitors; blood clotting parameters; drug effects; human; metabolism; neutrophil; phosphorylation; procedures; rabbit; signal transduction; thrombocyte; thrombocyte aggregation; 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Animals; Arachidonic Acid; Blood Platelets; Catechols; Cyclooxygenase Inhibitors; Humans; MAP Kinase Signaling System; Neutrophils; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prostaglandin-Endoperoxide Synthases; Rabbits; Reactive Oxygen Species; Thromboxane A2
Publisher
Public Library of Science
Type
journal article