dc.contributor.author | Pennell, Evan Noel | |
dc.contributor.author | Wagner, Karl-Heinz | |
dc.contributor.author | Mosawy, Sapha | |
dc.contributor.author | Bulmer, Andrew Cameron | |
dc.date.accessioned | 2019-07-11T12:32:00Z | |
dc.date.available | 2019-07-11T12:32:00Z | |
dc.date.issued | 2019 | |
dc.identifier.issn | 2213-2317 | |
dc.identifier.doi | 10.1016/j.redox.2019.101250 | |
dc.identifier.uri | http://hdl.handle.net/10072/385899 | |
dc.description.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 H2DCFDA 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. | |
dc.description.peerreviewed | Yes | |
dc.language | English | |
dc.language.iso | eng | |
dc.publisher | Elsevier | |
dc.relation.ispartofchapter | 101250 | |
dc.relation.ispartofpagefrom | 101250 | |
dc.relation.ispartofpageto | 101250 | |
dc.relation.ispartofjournal | Redox Biology | |
dc.relation.ispartofvolume | 26 | |
dc.subject.fieldofresearch | Biochemistry and cell biology | |
dc.subject.fieldofresearch | Medical biochemistry and metabolomics | |
dc.subject.fieldofresearch | Haematology | |
dc.subject.fieldofresearch | Pharmacology and pharmaceutical sciences | |
dc.subject.fieldofresearchcode | 3101 | |
dc.subject.fieldofresearchcode | 3205 | |
dc.subject.fieldofresearchcode | 320102 | |
dc.subject.fieldofresearchcode | 3214 | |
dc.title | Acute bilirubin ditaurate exposure attenuates ex vivo platelet reactive oxygen species production, granule exocytosis and activation | |
dc.type | Journal article | |
dc.type.description | C1 - Articles | |
dc.type.code | C - Journal Articles | |
dcterms.license | http://creativecommons.org/licenses/BY-NC-ND/4.0/ | |
dc.description.version | Version of Record (VoR) | |
gro.rights.copyright | © 2019 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/). | |
gro.hasfulltext | Full Text | |
gro.griffith.author | Bulmer, Andrew C. | |