The anticoagulant effects of ethyl pyruvate in whole blood samples

Harald Haidl; Alex Schlagenhauf; Angelika Krebs; Harald Plank; Willibald Wonisch; Vera Fengler; Gerd Hörl; Martin Köstenberger; Thomas Wagner; Gerhard Cvirn; Seth Hallstrom; Erwin Tafelt

doi:10.1371/journal.pone.0240541

The anticoagulant effects of ethyl pyruvate in whole blood samples

Harald Haidl, Alex Schlagenhauf, Angelika Krebs, Harald Plank, Willibald Wonisch, Vera Fengler, Gerd Hörl, Martin Köstenberger, Thomas Wagner, Gerhard Cvirn^*, Seth Hallstrom, Erwin Tafelt

^*Corresponding author for this work

Institute of Electron Microscopy and Nanoanalysis (5190)

Research output: Contribution to journal › Article › peer-review

Abstract

Background Ethyl pyruvate (EP), the ethyl ester of pyruvate, has proven antiinflammatory and antioxidative properties. Additionally, anticoagulant properties have been suggested recently. EP, therefore, is a potentially antiatherosclerotic drug. We aimed to investigate whether EP possesses antiplatelet and anticoagulant properties particularly in the physiological environment of whole blood. Methods We investigated the effects of increasing concentrations of EP on platelet function, on the course of clot development, and on standard coagulation times. Additionally, clot ultrastructure using scanning electron microscopy was analysed. Results EP exerted significant antiplatelet actions: I) Impedance aggregometry amplitudes (11.7 ± 3.0 ohm, 0 μg/mL EP) dose dependently decreased (7.8 ± 3.1 ohm, 1000 μg/mL EP; -33.3%). ATP exocytosis (0.87 ± 0.24 nM, 0 μg/mL EP) measured by the luminiscent method dose-dependently decreased (0.56 ± 0.14 nM, 1000 μg/mL; -35.6%). ii) Closure times (104.4 ± 23.8 s, 0 μg/mL EP) using the Platelet function analyzer were dose-dependently prolonged (180.5 ± 82.5 s, 1000 μg/mL EP; +72.9%) using membranes coated with collagen/ADP. iii) Surface coverage (15.9 ± 5.1%, 0 μg/mL EP) dose-dependently decreased (9.0 ± 3.7%, 1000 μg/mL EP; -43.4%) using the Cone and Platelet analyzer. EP also exerted significant anticoagulant actions: Coagulation times (177.9 ± 37.8, 0 μg/mL EP) evaluated by means of thrombelastometry were dose-dependently prolonged (212.8 ± 57.7 s, 1000 μg/mL EP; +19.6%). Activated partial thromboplastin times (31.5 ± 1.8 s, 0 μg/ mL EP) were dose-dependently prolonged (35.6 ± 2.3 s, 1000 μg/mL EP; +13.0%). Prothrombin times (0.94 ± 0.02 INR, 0 μg/mL EP) were dose-dependently prolonged (1.09 ± 0.04 INR, 1000 μg/mL EP; +16.0%). Conclusion We found that EP possesses antiplatelet and anticoagulant properties in whole blood. Together with its proven anti-inflammatory and antioxidative properties, EP is a potentially antiatherogenic drug.

Original language	English
Article number	e0240541
Number of pages	17
Journal	PLoS ONE
Volume	15
Issue number	9 October
DOIs	https://doi.org/10.1371/journal.pone.0240541
Publication status	Published - 9 Oct 2020

ASJC Scopus subject areas

General Materials Science

Fields of Expertise

Advanced Materials Science

Treatment code (Nähere Zuordnung)

Basic - Fundamental (Grundlagenforschung)

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10.1371/journal.pone.0240541Licence: CC BY 4.0

Cite this

@article{50d3b3d5dfa84b82a5e6a4034b7b2c84,

title = "The anticoagulant effects of ethyl pyruvate in whole blood samples",

abstract = "Background Ethyl pyruvate (EP), the ethyl ester of pyruvate, has proven antiinflammatory and antioxidative properties. Additionally, anticoagulant properties have been suggested recently. EP, therefore, is a potentially antiatherosclerotic drug. We aimed to investigate whether EP possesses antiplatelet and anticoagulant properties particularly in the physiological environment of whole blood. Methods We investigated the effects of increasing concentrations of EP on platelet function, on the course of clot development, and on standard coagulation times. Additionally, clot ultrastructure using scanning electron microscopy was analysed. Results EP exerted significant antiplatelet actions: I) Impedance aggregometry amplitudes (11.7 ± 3.0 ohm, 0 μg/mL EP) dose dependently decreased (7.8 ± 3.1 ohm, 1000 μg/mL EP; -33.3%). ATP exocytosis (0.87 ± 0.24 nM, 0 μg/mL EP) measured by the luminiscent method dose-dependently decreased (0.56 ± 0.14 nM, 1000 μg/mL; -35.6%). ii) Closure times (104.4 ± 23.8 s, 0 μg/mL EP) using the Platelet function analyzer were dose-dependently prolonged (180.5 ± 82.5 s, 1000 μg/mL EP; +72.9%) using membranes coated with collagen/ADP. iii) Surface coverage (15.9 ± 5.1%, 0 μg/mL EP) dose-dependently decreased (9.0 ± 3.7%, 1000 μg/mL EP; -43.4%) using the Cone and Platelet analyzer. EP also exerted significant anticoagulant actions: Coagulation times (177.9 ± 37.8, 0 μg/mL EP) evaluated by means of thrombelastometry were dose-dependently prolonged (212.8 ± 57.7 s, 1000 μg/mL EP; +19.6%). Activated partial thromboplastin times (31.5 ± 1.8 s, 0 μg/ mL EP) were dose-dependently prolonged (35.6 ± 2.3 s, 1000 μg/mL EP; +13.0%). Prothrombin times (0.94 ± 0.02 INR, 0 μg/mL EP) were dose-dependently prolonged (1.09 ± 0.04 INR, 1000 μg/mL EP; +16.0%). Conclusion We found that EP possesses antiplatelet and anticoagulant properties in whole blood. Together with its proven anti-inflammatory and antioxidative properties, EP is a potentially antiatherogenic drug.",

author = "Harald Haidl and Alex Schlagenhauf and Angelika Krebs and Harald Plank and Willibald Wonisch and Vera Fengler and Gerd H{\"o}rl and Martin K{\"o}stenberger and Thomas Wagner and Gerhard Cvirn and Seth Hallstrom and Erwin Tafelt",

year = "2020",

month = oct,

day = "9",

doi = "10.1371/journal.pone.0240541",

language = "English",

volume = "15",

journal = "PLoS ONE",

publisher = "Public Library of Science",

number = "9 October",

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TY - JOUR

T1 - The anticoagulant effects of ethyl pyruvate in whole blood samples

AU - Haidl, Harald

AU - Schlagenhauf, Alex

AU - Krebs, Angelika

AU - Plank, Harald

AU - Wonisch, Willibald

AU - Fengler, Vera

AU - Hörl, Gerd

AU - Köstenberger, Martin

AU - Wagner, Thomas

AU - Cvirn, Gerhard

AU - Hallstrom, Seth

AU - Tafelt, Erwin

PY - 2020/10/9

Y1 - 2020/10/9

N2 - Background Ethyl pyruvate (EP), the ethyl ester of pyruvate, has proven antiinflammatory and antioxidative properties. Additionally, anticoagulant properties have been suggested recently. EP, therefore, is a potentially antiatherosclerotic drug. We aimed to investigate whether EP possesses antiplatelet and anticoagulant properties particularly in the physiological environment of whole blood. Methods We investigated the effects of increasing concentrations of EP on platelet function, on the course of clot development, and on standard coagulation times. Additionally, clot ultrastructure using scanning electron microscopy was analysed. Results EP exerted significant antiplatelet actions: I) Impedance aggregometry amplitudes (11.7 ± 3.0 ohm, 0 μg/mL EP) dose dependently decreased (7.8 ± 3.1 ohm, 1000 μg/mL EP; -33.3%). ATP exocytosis (0.87 ± 0.24 nM, 0 μg/mL EP) measured by the luminiscent method dose-dependently decreased (0.56 ± 0.14 nM, 1000 μg/mL; -35.6%). ii) Closure times (104.4 ± 23.8 s, 0 μg/mL EP) using the Platelet function analyzer were dose-dependently prolonged (180.5 ± 82.5 s, 1000 μg/mL EP; +72.9%) using membranes coated with collagen/ADP. iii) Surface coverage (15.9 ± 5.1%, 0 μg/mL EP) dose-dependently decreased (9.0 ± 3.7%, 1000 μg/mL EP; -43.4%) using the Cone and Platelet analyzer. EP also exerted significant anticoagulant actions: Coagulation times (177.9 ± 37.8, 0 μg/mL EP) evaluated by means of thrombelastometry were dose-dependently prolonged (212.8 ± 57.7 s, 1000 μg/mL EP; +19.6%). Activated partial thromboplastin times (31.5 ± 1.8 s, 0 μg/ mL EP) were dose-dependently prolonged (35.6 ± 2.3 s, 1000 μg/mL EP; +13.0%). Prothrombin times (0.94 ± 0.02 INR, 0 μg/mL EP) were dose-dependently prolonged (1.09 ± 0.04 INR, 1000 μg/mL EP; +16.0%). Conclusion We found that EP possesses antiplatelet and anticoagulant properties in whole blood. Together with its proven anti-inflammatory and antioxidative properties, EP is a potentially antiatherogenic drug.

AB - Background Ethyl pyruvate (EP), the ethyl ester of pyruvate, has proven antiinflammatory and antioxidative properties. Additionally, anticoagulant properties have been suggested recently. EP, therefore, is a potentially antiatherosclerotic drug. We aimed to investigate whether EP possesses antiplatelet and anticoagulant properties particularly in the physiological environment of whole blood. Methods We investigated the effects of increasing concentrations of EP on platelet function, on the course of clot development, and on standard coagulation times. Additionally, clot ultrastructure using scanning electron microscopy was analysed. Results EP exerted significant antiplatelet actions: I) Impedance aggregometry amplitudes (11.7 ± 3.0 ohm, 0 μg/mL EP) dose dependently decreased (7.8 ± 3.1 ohm, 1000 μg/mL EP; -33.3%). ATP exocytosis (0.87 ± 0.24 nM, 0 μg/mL EP) measured by the luminiscent method dose-dependently decreased (0.56 ± 0.14 nM, 1000 μg/mL; -35.6%). ii) Closure times (104.4 ± 23.8 s, 0 μg/mL EP) using the Platelet function analyzer were dose-dependently prolonged (180.5 ± 82.5 s, 1000 μg/mL EP; +72.9%) using membranes coated with collagen/ADP. iii) Surface coverage (15.9 ± 5.1%, 0 μg/mL EP) dose-dependently decreased (9.0 ± 3.7%, 1000 μg/mL EP; -43.4%) using the Cone and Platelet analyzer. EP also exerted significant anticoagulant actions: Coagulation times (177.9 ± 37.8, 0 μg/mL EP) evaluated by means of thrombelastometry were dose-dependently prolonged (212.8 ± 57.7 s, 1000 μg/mL EP; +19.6%). Activated partial thromboplastin times (31.5 ± 1.8 s, 0 μg/ mL EP) were dose-dependently prolonged (35.6 ± 2.3 s, 1000 μg/mL EP; +13.0%). Prothrombin times (0.94 ± 0.02 INR, 0 μg/mL EP) were dose-dependently prolonged (1.09 ± 0.04 INR, 1000 μg/mL EP; +16.0%). Conclusion We found that EP possesses antiplatelet and anticoagulant properties in whole blood. Together with its proven anti-inflammatory and antioxidative properties, EP is a potentially antiatherogenic drug.

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U2 - 10.1371/journal.pone.0240541

DO - 10.1371/journal.pone.0240541

M3 - Article

VL - 15

JO - PLoS ONE

JF - PLoS ONE

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M1 - e0240541

ER -

The anticoagulant effects of ethyl pyruvate in whole blood samples

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