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dc.contributor.authorPennell, Evan Noel
dc.contributor.authorWagner, Karl-Heinz
dc.contributor.authorMosawy, Sapha
dc.contributor.authorBulmer, Andrew Cameron
dc.date.accessioned2019-07-11T12:32:00Z
dc.date.available2019-07-11T12:32:00Z
dc.date.issued2019
dc.identifier.issn2213-2317
dc.identifier.doi10.1016/j.redox.2019.101250
dc.identifier.urihttp://hdl.handle.net/10072/385899
dc.description.abstractBackground: 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.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherElsevier
dc.relation.ispartofchapter101250
dc.relation.ispartofpagefrom101250
dc.relation.ispartofpageto101250
dc.relation.ispartofjournalRedox Biology
dc.relation.ispartofvolume26
dc.subject.fieldofresearchBiochemistry and cell biology
dc.subject.fieldofresearchMedical biochemistry and metabolomics
dc.subject.fieldofresearchHaematology
dc.subject.fieldofresearchPharmacology and pharmaceutical sciences
dc.subject.fieldofresearchcode3101
dc.subject.fieldofresearchcode3205
dc.subject.fieldofresearchcode320102
dc.subject.fieldofresearchcode3214
dc.titleAcute bilirubin ditaurate exposure attenuates ex vivo platelet reactive oxygen species production, granule exocytosis and activation
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dcterms.licensehttp://creativecommons.org/licenses/BY-NC-ND/4.0/
dc.description.versionVersion 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.hasfulltextFull Text
gro.griffith.authorBulmer, Andrew C.


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