Inhibition of platelet aggregation and arachidonic acid metabolism by B-carboline alkaloids

1993 ◽  
Vol 21 (4) ◽  
pp. 461S-461S ◽  
Author(s):  
SHEIKH A. SAEED ◽  
RUKHSANA U. SIMJEE ◽  
SAMINA FARNAZ ◽  
ANWAR H. GILANI ◽  
SALIMUZZAMAN SIDDIQUI ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Acid Metabolism ◽  
Arachidonic Acid Metabolism ◽  
Inhibition Of Platelet Aggregation

Influence of certain compounds of plant origin on platelet aggregation and arachidonic acid metabolism in human platelets

1986 ◽  
Vol 20 (10) ◽  
pp. 740-744
Author(s):  
A. G. Panosyan ◽  
A. G. Aivazyan ◽  
M. L. Barikyan ◽  
G. A. Gevorkyan ◽  
G. G. Zapesochnaya ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Acid Metabolism ◽  
Human Platelets ◽  
Arachidonic Acid Metabolism ◽  
Plant Origin

Superoxide Anion and Hydroxyl Radical Release by Collagen-induced Platelet Aggregation - Role of Arachidonic Acid Metabolism

2000 ◽  
Vol 83 (03) ◽  
pp. 485-490 ◽  
Author(s):  
Daniela Caccese ◽  
Domenico Praticò ◽  
Andrea Ghiselli ◽  
Silvia Natoli ◽  
Pasquale Pignatelli ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Salicylic Acid ◽  
Platelet Aggregation ◽  
Hydroxyl Radical ◽  
Superoxide Anion ◽  
Acid Metabolism ◽  
Arachidonic Acid Metabolism ◽  
Cytosolic Phospholipase ◽  
Generate Superoxide Anion

SummaryPrevious study demonstrated that platelets undergoing anoxia-reoxygenation generate superoxide anion (O2 −) and hydroxyl radical (OH°) which in turn contribute to activate arachidonic acid (AA) metabolism. However it has not been clarified if oxygen free radicals (OFRs) are also generated when platelets are aggregated by common agonists. We used two probes, i.e. lucigenin and salicylic acid (SA), to measure platelet release of O2 − and OH°, respectively. Among the agonists used, such as ADP, thrombin and collagen, the release of O2 − and OH° was observed mainly when platelets were stimulated with collagen. Such release was inhibited in platelets pre-treated by aspirin suggesting that AA metabolism was the main source of O2 − and OH° formation. To further analyze this relationship, O2 and OH° formation was measured if other oxidant species, namely O2 − and OH°, contribute to the during AA-stimulated platelet aggregation (PA); we observed that O − and OH° release were dependent upon AA concentration. Furthermore, we found that the incubation of platelets with AACOCF3, a potent inhibitor of cytosolic phospholipase A2, inhibited collagen-induced platelet O− and OH° release. The incubation of platelets with salicylic acid or ascorbic acid, which blunt OH° and O2 − respectively, inhibited both collagen-induced platelet aggregation and AA-release. This study demonstrated that collagen-induced platelet aggregation is associated with O2 − and OH° formation, which is dependent upon AA release and analyzed if O2 − and OH° are released during aggregation induced by metabolism.

CYCLOOXYGENASE AND LIPOXYGENASE PRODUCTS SYNERGISTICALLY MODULATE TUMOR CELL INDUCED PLATELET AGGREGATION

1987 ◽  
Author(s):  
Bruce W Steinert ◽  
James M Onoda ◽  
Bonnie F Sloane ◽  
John D Taylor ◽  
Kenneth V Honn
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Tumor Cell ◽  
Acid Metabolism ◽  
Platelet Rich Plasma ◽  
Arachidonic Acid Metabolism ◽  
Cyclooxygenase Inhibitors ◽  
Dependent Manner ◽  
Lipoxygenase Inhibitors ◽  
Agonist Concentration

There has been considerable controversy surrounding the ability of inhibitors of arachidonic acid metabolism to concomitantly inhibit tumor cell induced platelet aggregation (TCIPA). Reconciliation of this controversy has been difficult due to the wide variability of experimental conditions (e.g., inhibitor concentration, strength of the inducing agonist).In the present study, we examined the effects of several cyclooxygenaseand lipoxygenase inhibitors on the induction of platelet aggregation by Walker 256 carcinosarcoma (W256) cells. We have previously demonstrated that aggregation of platelet rich plasma (PRP), induced by W256 cells, was initiated via a thrombin dependent mechanism. Platelet aggregation was induced by the addition of W256 cells (75,000-J500,000 cells/cuvette) to rat PRP preincubated with inhibitor(s) or diluent. The strength of the inducing stimulus affected both the degree of aggregation and the production of thromboxane A2 (TXA2) in a dose dependent manner. A weak stimulus (low concentration of W256 cells) produced only a low level of aggregation and low TXA2 production, whereas aggregation induced by a strong stimulus (high concentration of W256 cells) resulted in significant aggregation and increased TXA2 production. Preincubation (5 min., 37°C) of rat PRP with cyclooxygenase inhibitors (e.g., aspirin, indomethacin, ibuprofen) resulted in complete inhibition of platelet aggregation at low agonist concentration (75,000 W256 cells), whereas when a high agonist concentration (500,000 W256 cells) was used to induce aggregation, the inhibitors failed to inhibit TCIPA. The addition of fewer than 50,000W256 cells failed to induce any measurable platelet aggregation in the presence or absence of inhibitors. TCIPA was not affected by lipoxygenaseinhibitors (e.g.,quercetin) alone regardless of agonist concentration. Both cyclooxygenase and lipoxygenase inhibitors, however, were required to significantly inhibit TCIPA induced by high agonist concentration. Compounds which inhibited both the cycloogygenase and lipoxygenase pathways (e.g.,hydroquinone, BW755c) inhibited TCIPA at all agonist concentrations. Nafazatrom failed to inhibit TCIPA consistant with a lack of effect on platelet cyclooxygenase and lipoxygenase. Therefore, we conclude cyclooxygenase (e.g., TXA2) and lipoxygenase (e.g., 12-HETE) products of platelet arachidonic acid metabolism and the strength of the inducingagonist are important criteria in TCIPA. This study may help to clarify the current controversy regarding the inhibition of TCIPA by inhibitors of arachidonic acid metabolism.

scholarly journals Arachidonic Acid Metabolism of Platelet in Diabetes

1977 ◽  
Author(s):  
T. Kurosawa ◽  
T. Tojima ◽  
H. Funayama ◽  
Y. Takahashi ◽  
Y. Shiokawa
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Sodium Citrate ◽  
Acid Metabolism ◽  
Platelet Rich Plasma ◽  
Normal Subjects ◽  
Arachidonic Acid Metabolism ◽  
Gas Liquid Chromatography ◽  
Glucose Loading ◽  
Freeze Dried

Recent reports have indicated that platelet aggregation is enhanced in some diabetics who have proliferative retinopathy and that platelet function is a altered by glucose loading. But the mechanism is not clarified yet. Arachidonic acid, the precursor of prostaglandin endoperoxide, plays a major role on platelet aggregation. Blood samples were collected with sodium citrate at 0, 30, 60, 120 and 300 minutes after 100 g glucose loading. Platelet-rich plasma was obtained by centrifugation and platelet aggregation was studied photometrically adding ADP. Platelet was obtained by further centrifugation and was kept freeze-dried. Platelet samples were extracted and transesterificated and separated by gas liquid chromatography. The quantitative regulation of arachidonic acid in platelets was measured by the composition ratio of arachidonic acid (C20-4)/linoleic acid (C18-2)=AL index. The results of platelet aggregation after glucose loading were as follows; platelet aggregation was not changed remarkably in normal subjects, but was enhanced at 30 and 60 and suppressed at 120 minutes in diabetics.AL index is as fol lows:prior to glucose loading, AL index of diabetics (4.6 ± 1.2) was higher than that of normal subjects (3.5 ± 0.5). After glucose loading, no significant change was observed in normal subjects, but AL index was increased at 30 (4.8 ± 1.4) and 60 (4.9 ± 1.4) and decreased at 120 minutes (4.1 ± 0.9) in diabetics. The results indicates that there is a certain relationship between quantitative regulation of arachidonic acid in platelet and platelet aggregation and that hyperaggregation may be induced by abnormal prostaglandin metabolism in diabetes.

scholarly journals Hydrogen Peroxide Is Involved in Collagen-Induced Platelet Activation

Blood ◽  
1998 ◽  
Vol 91 (2) ◽  
pp. 484-490 ◽  
Author(s):  
Pasquale Pignatelli ◽  
Fabio M. Pulcinelli ◽  
Luisa Lenti ◽  
Pier Paolo Gazzaniga ◽  
Francesco Violi
Keyword(s):  
Hydrogen Peroxide ◽  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Phospholipase C ◽  
Platelet Activation ◽  
Acid Metabolism ◽  
Thromboxane A2 ◽  
Arachidonic Acid Metabolism ◽  
H2o2 Production ◽  
High Concentrations

Abstract In this study, we investigated whether (1) collagen-induced platelet aggregation is associated with a burst of H2O2, (2) this oxidant species is involved in the activation of platelets, and (3) the pathways of platelet activation are stimulated by H2O2. Collagen-induced platelet aggregation was associated with production of H2O2, which was abolished by catalase, an enzyme that destroys H2O2. H2O2 production was not observed when ADP or thrombin were used as agonists. Catalase inhibited dose-dependently thromboxane A2 production, release of arachidonic acid from platelet membrane, and Inositol 1,4,5P3 (IP3) formation. In aspirin-treated platelets stimulated with high concentrations of collagen, catalase inhibited platelet aggregation, calcium mobilization, and IP3 production. This study suggests that collagen-induced platelet aggregation is associated with a burst of H2O2 that acts as a second messenger by stimulating the arachidonic acid metabolism and phospholipase C pathway.

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