Salicylate fails to prevent the inhibitory effect of 5,8,11,14-eicosatetraynoic acid on human platelet cyclo-oxygenase and lipoxygenase activities

Cerletti, Chiara; Livio, M.; Doni, Maria Gabriella; Gaetano, Giovanni de

doi:10.1016/0304-4165(83)90197-6

Cited by 18 publications

(6 citation statements)

References 8 publications

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“…Both salicylic and gallic acid bind to Arg120 with similar interaction energies, most likely by their carboxyl group. This structural observation is consistent with our pharmacological data showing that both salicylic and gallic acid, that have little if any COX-1 inhibitory activity by themselves, antagonize aspirin inhibition of the enzyme (33,34).…”

Section: Discussionsupporting

confidence: 92%

Interactions of gallic acid, resveratrol, quercetin and aspirin at the platelet cyclooxygenase-1 level Functional and modelling studies

Crescente

Jessen²,

Momi³

et al. 2009

Thromb Haemost

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While resveratrol and quercetin possess antiplatelet activity, little is known on the effect of gallic acid on platelets. We studied the interactions of these three different polyphenols among themselves and with aspirin, at the level of platelet cyclooxygenase-1 (COX-1). Both functional (in vitro and in vivo) and molecular modelling approaches were used. All three polyphenols showed comparable antioxidant activity (arachidonic acid [AA]-induced intraplatelet ROS production); however, resveratrol and quercetin, but not gallic acid, inhibited AA-induced platelet aggregation. Gallic acid, similarly to salicylic acid, the major aspirin metabolite, prevented inhibition of AA-induced platelet function by aspirin but, at variance with salicylic acid, also prevented inhibition by the other two polyphenols. Molecular modelling studies, performed by in silico docking the polyphenols into the crystal structure of COX-1, suggested that all compounds form stable complexes into the COX-1 channel, with slightly different but functionally relevant interaction geometries. Experiments in mice showed that gallic acid administered before aspirin, resveratrol or quercetin fully prevented their inhibitory effect on serum TxB(2). Finally, a mixture of resveratrol, quercetin and gallic acid, at relative concentrations similar to those contained in most red wines, did not inhibit platelet aggregation, but potentiated sub-inhibitory concentrations of aspirin. Gallic acid interactions with other polyphenols or aspirin at the level of platelet COX-1 might partly explain the complex, and possibly contrasting, effects of wine and other components of the Mediterranean diet on platelets and on the pharmacologic effect of low-dose aspirin.

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Section: Discussionsupporting

confidence: 92%

Interactions of gallic acid, resveratrol, quercetin and aspirin at the platelet cyclooxygenase-1 level Functional and modelling studies

Crescente

Jessen²,

Momi³

et al. 2009

Thromb Haemost

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“…Aspirin pretreatment inhibited PGE2 production by human PMNs and eosinophils in either vehicle-or cis-fatty acidstimulated leukocytes (data not shown), but this inhibition might be due solely to aspirin inhibition of COX. In contrast, aspirin is devoid of direct inhibitory effects upon lipoxygenases in leukocytes and platelets (37)(38)(39). We found that aspirin significantly inhibited AA-and OA-induced priming for enhanced production of 5-lipoxygenase-derived LTB4 by PMNs (Fig.…”

Section: Resultsmentioning

confidence: 71%

Leukocyte lipid body formation and eicosanoid generation: cyclooxygenase-independent inhibition by aspirin.

Bozza

Payne

Morham³

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

112

123

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Lipid bodies, cytoplasmic inclusions that develop in cells associated with inflammation, are inducible structures that might participate in generating inflammatory eicosanoids. Cis-unsaturated fatty acids (arachidonic and oleic acids) rapidly induced lipid body formation in leukocytes, and this lipid body induction was inhibited by aspirin and nonsteroidal antiinflammatory drugs (NSAIDs). Several findings indicated that the inhibitory effect of aspirin and NSAIDs on lipid body formation was independent of cyclooxygenase (COX) inhibition. First, the non-COX inhibitor, sodium salicylate, was as potent as aspirin in inhibiting lipid body formation elicited by cis-fatty acids. Second, cis-fatty acid-induced lipid body formation was not impaired in macrophages from COX-1 or COX-2 genetically deficient mice. Finally, NSAIDs inhibited arachidonic acid-induced lipid body formation likewise in macrophages from wild-type and COX-1-and COX-2-deficient mice. An enhanced capacity to generate eicosanoids developed after 1 hr concordantly with cis-fatty acid-induced lipid body formation. Arachidonic and oleic acid-induced lipid body numbers correlated with the enhanced levels of leukotrienes B4 and C4 and prostaglandin E2 produced after submaximal calcium ionophore stimulation. Aspirin and NSAIDs inhibited both induced lipid body formation and the enhanced capacity for forming leukotrienes as well as prostaglandins. Our studies indicate that lipid body formation is an inducible early response in leukocytes that correlates with enhanced eicosanoid synthesis. Aspirin and NSAIDs, independent of COX inhibition, inhibit cis-fatty acid-induced lipid body formation in leukocytes and in concert inhibit the enhanced synthesis of leukotrienes and prostaglandins.

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“…These results suggest an involvement of the platelet lipoxygenase in mediating the aggregation induced by canatoxin, independent ofcyclo-oxygenase products. This hypothesis was further reinforced with NDGA, a lipoxygenasespecific blocker (Hamberg, 1976;Higgs & Vane, 1983;Cerletti et al, 1983), which inhibited the canatoxininduced aggregation. Although these lipoxygenase blockers could be also exerting an as yet unsuspected lipoxygenase-independent effect, their action seemed to be selective for canatoxin, since aggregation by Pafacether was not prevented by any of these agents.…”

Section: Discussionmentioning

confidence: 93%

Platelet release reaction and aggregation induced by canatoxin, a convulsant protein: evidence for the involvement of the platelet lipoxygenase pathway

Carlini

Guimarães

Ribeiro

1985

British J Pharmacology

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Canatoxin is a toxic protein isolated from Canavalia ensiformis seeds. It induces death preceded by convulsions of spinal cord origin and also produces in vitro aggregation of platelets in rabbit, human and guinea‐pig plasma. The aggregating effect is dose‐dependent at nanomolar concentrations. Rabbit platelets pretreated with canatoxin became refractory to a second exposure to this protein or to collagen, but were still responsive to ADP, Paf‐acether or arachidonic acid. [14C]‐5‐hydroxytryptamine was released from pre‐labelled platelets on stimulation with canatoxin. Washed rabbit platelets, but not thrombin‐degranulated ones, aggregated on stimulation with canatoxin provided that fibrinogen was added before the toxin. Canatoxin's pro‐aggregating activity was inhibited by mepacrine, EDTA, caffeine, prostacyclin, adenosine monophosphate and also by the ADP scavenger system, creatine phosphokinase/creatine phosphate. Furthermore, 3‐amino‐l‐[m‐(trifluoromethyl)‐phenyl]‐2‐pyrazoline (BW 755C), eicosatetraynoic acid (ETYA) and nordihydroguaiaretic acid (NDGA) were potent inhibitors of canatoxin‐induced aggregation. In contrast, no inhibition was seen with indomethacin. The data indicate that canatoxin is mainly a release‐reaction‐promoting agent, being devoid of any direct aggregating activity. Thus the aggregation is totally dependent on the release of ADP. Furthermore, canatoxin‐induced platelet activation is probably dependent on platelet phospholipase A2 and lipoxygenase activity but is not dependent on cyclo‐oxygenase products or the release of Paf‐acether.

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Salicylate fails to prevent the inhibitory effect of 5,8,11,14-eicosatetraynoic acid on human platelet cyclo-oxygenase and lipoxygenase activities

Cited by 18 publications

References 8 publications

Interactions of gallic acid, resveratrol, quercetin and aspirin at the platelet cyclooxygenase-1 level Functional and modelling studies

Interactions of gallic acid, resveratrol, quercetin and aspirin at the platelet cyclooxygenase-1 level Functional and modelling studies

Leukocyte lipid body formation and eicosanoid generation: cyclooxygenase-independent inhibition by aspirin.

Platelet release reaction and aggregation induced by canatoxin, a convulsant protein: evidence for the involvement of the platelet lipoxygenase pathway

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