Inhibitory effects of ethyl pyruvate on platelet aggregation and phosphatidylserine exposure

Biochem Biophys Res Commun. 2017 Jun 3;487(3):560-566. doi: 10.1016/j.bbrc.2017.04.087. Epub 2017 Apr 18.

Abstract

Ethyl pyruvate (EP) is a stable lipophilic pyruvate derivative. Studies demonstrated that EP shows potent anti-oxidation, anti-inflammatory and anti-coagulant effects. Inflammation and coagulation are closely interacted with platelet activation. However, it is unclear whether EP has anti-platelet effects. Therefore, we investigated the anti-platelet effect of EP in this study in vitro. We found that EP inhibited agonists induced platelets aggregation, ATP release and adhesion to collagen. Flow cytometric analysis revealed that EP inhibited agonist induced platelets PAC-1 binding, as well as P-selectin and CD40L expression. The underlying mechanism of action may involve the inhibition of platelet PI3K/Akt and Protein Kinase C (PKC) signaling pathways. Additionally, EP dose dependently inhibited platelet PS exposure induced by high concentration thrombin. Lactate dehydrogenase (LDH) activity assay and mice platelet count implied that EP may have no toxic effect on platelets. Therefore, we are the first to report that EP has potent anti-platelet activity and attenuates platelet PS exposure in vitro, suggesting that the inhibitory effects of EP on platelets may also play important roles in improvement of inflammation and coagulation disorder in related animal models.

Keywords: Coagulation; Ethyl pyruvate; Inflammation; Phosphatidylserine exposure; Platelet activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / antagonists & inhibitors
  • Adenosine Triphosphate / metabolism
  • Animals
  • Blood Proteins / pharmacology*
  • Collagen / antagonists & inhibitors
  • Collagen / pharmacology
  • Dose-Response Relationship, Drug
  • Female
  • Healthy Volunteers
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Phosphatidylserines / administration & dosage
  • Phosphatidylserines / antagonists & inhibitors*
  • Phosphatidylserines / pharmacology
  • Platelet Adhesiveness / drug effects
  • Platelet Aggregation / drug effects*
  • Pyruvates / pharmacology*
  • Structure-Activity Relationship
  • Thrombin / antagonists & inhibitors
  • Thrombin / pharmacology

Substances

  • Blood Proteins
  • Phosphatidylserines
  • Pyruvates
  • platelet adhesion inhibitor
  • ethyl pyruvate
  • Adenosine Triphosphate
  • Collagen
  • Thrombin