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Redox biology
09, 2019;26 101250.

Acute bilirubin ditaurate exposure attenuates ex vivo platelet reactive oxygen species production, granule exocytosis and activation.

Evan Noel Pennell, Karl-Heinz Wagner, Sapha Mosawy, Andrew Cameron Bulmer
Author Information
  1. Evan Noel Pennell: School of Medical Science, Griffith University, Gold Coast, Australia.
  2. Karl-Heinz Wagner: Research Platform Active Aging, Department of Nutritional Science, University of Vienna, Austria. Electronic address: karl-heinz.wagner@univie.ac.at.
  3. Sapha Mosawy: School of Medical Science, Griffith University, Gold Coast, Australia; Endeavour College of Natural Health, Melbourne, Australia.
  4. Andrew Cameron Bulmer: School of Medical Science, Griffith University, Gold Coast, Australia. Electronic address: a.bulmer@griffith.edu.au.
PMID: 31226648 DOI: 10.1016/j.redox.2019.101250

Abstract

BACKGROUND: Bilirubin, a by-product of haem catabolism, possesses potent endogenous antioxidant and platelet inhibitory properties. These properties may be useful in inhibiting inappropriate platelet activation and ROS production; for example, during storage for transfusion. Given the hydrophobicity of unconjugated bilirubin (UCB), we investigated the acute platelet inhibitory and ROS scavenging ability of a water-soluble bilirubin analogue, bilirubin ditaurate (BRT) on ex vivo platelet function to ascertain its potential suitability for inclusion during platelet storage.
METHODS: The inhibitory potential of BRT (10-100 μM) was assessed using agonist induced platelet aggregation, dense granule exocytosis and flow cytometric analysis of P-selectin and GPIIb/IIIa expression. ROS production was investigated by analysis of HDCFDA fluorescence following agonist simulation while mitochondrial ROS production investigated using MitoSOX™ Red. Platelet mitochondrial membrane potential and viability was assessed using TMRE and Zombie Green™ respectively.
RESULTS: Our data shows ≤35 μM BRT significantly inhibits both dense and alpha granule exocytosis as measured by ATP release and P-selectin surface expression, respectively. Significant inhibition of GPIIb/IIIa expression was also reported upon ≤35 μM BRT exposure. Furthermore, platelet exposure to ≤10 μM BRT significantly reduces platelet mitochondrial ROS production. Despite the inhibitory effect of BRT, platelet viability, mitochondrial membrane potential and agonist induced aggregation were not perturbed.
CONCLUSIONS: These data indicate, for the first time, that BRT, a water-soluble bilirubin analogue, inhibits platelet activation and reduces platelet ROS production ex vivo and may, therefore, may be of use in preserving platelet function during storage.

Keywords

Bilirubin ditaurate Flow cytometry MitoSOX™ Red Platelets ROS Superoxide

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MeSH Term

Adolescent
Adult
Alprostadil
Antioxidants
Bilirubin
Blood Platelets
Cell Survival
Cytoplasmic Granules
Exocytosis
Female
Gene Expression
Humans
Male
Membrane Potential, Mitochondrial
Middle Aged
Mitochondria
P-Selectin
Peptide Fragments
Platelet Activation
Platelet Aggregation
Platelet Glycoprotein GPIIb-IIIa Complex
Primary Cell Culture
Reactive Oxygen Species
Taurine

Chemicals

Antioxidants
P-Selectin
Peptide Fragments
Platelet Glycoprotein GPIIb-IIIa Complex
Reactive Oxygen Species
thrombin receptor peptide (42-47)
Taurine
bilirubin ditaurine
Alprostadil
Bilirubin
Journal Article Research Support, Non-U.S. Gov't
Article has an altmetric score of 1

Word Cloud

Created with Highcharts 10.0.0plateletROSBRTproductionbilirubininhibitorypotentialmitochondrialmayactivationstorageinvestigatedditaurateexvivousingagonistgranuleexocytosisexpressionexposureBilirubinpropertieswater-solubleanaloguefunctionassessedinducedaggregationdenseanalysisP-selectinGPIIb/IIIaMitoSOX™Redmembraneviabilityrespectivelydata≤35 μMsignificantlyinhibitsreducesBACKGROUND:by-producthaemcatabolismpossessespotentendogenousantioxidantusefulinhibitinginappropriateexampletransfusionGivenhydrophobicityunconjugatedUCBacutescavengingabilityascertainsuitabilityinclusionMETHODS:10-100 μMflowcytometricHDCFDAfluorescencefollowingsimulationPlateletTMREZombieGreen™RESULTS:showsalphameasuredATPreleasesurfaceSignificantinhibitionalsoreporteduponFurthermore≤10 μMDespiteeffectperturbedCONCLUSIONS:indicatefirsttimethereforeusepreservingAcuteattenuatesreactiveoxygenspeciesFlowcytometryPlateletsSuperoxide

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