Reactivity and speciation of anti-diabetic vanadium complexes in whole blood and its components: the important role of red blood cells

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dc.contributor.authorLevina, A.
dc.contributor.authorMcLeod, A.
dc.contributor.authorGasparini, S.
dc.contributor.authorNguyen, A.
dc.contributor.authorDe Silva, W.
dc.contributor.authorAitken, J.
dc.contributor.authorHarris, H.
dc.contributor.authorGlover, C.
dc.contributor.authorJohannessen, B.
dc.contributor.authorLay, P.
dc.date.issued2015
dc.description.abstractReactions with blood components are crucial for controlling the antidiabetic, anticancer, and other biological activities of V(V) and V(IV) complexes. Despite extensive studies of V(V) and V(IV) reactions with the major blood proteins (albumin and transferrin), reactions with whole blood and red blood cells (RBC) have been studied rarely. A detailed speciation study of Na3[V(V)O4] (A), K4[V(IV)2O2(citr)2]·6H2O (B; citr = citrato(4-)); [V(IV)O(ma)2] (C; ma = maltolato(-)), and (NH4)[V(V)(O)2(dipic)] (D; dipic = pyridine-2,6-dicarboxylato(2-)) in whole rat blood, freshly isolated rat plasma, and commercial bovine serum using X-ray absorption near-edge structure (XANES) spectroscopy is reported. The latter two compounds are potential oral antidiabetic drugs, and the former two are likely to represent their typical decomposition products in gastrointestinal media. XANES spectral speciation was performed by principal component analysis and multiple linear regression techniques, and the distribution of V between RBC and plasma fractions was measured by electrothermal atomic absorption spectroscopy. Reactions of A, C, or D with whole blood (1.0 mM V, 1-6 h at 310 K) led to accumulation of ∼50% of total V in the RBC fraction (∼10% in the case of B), which indicated that RBC act as V carriers to peripheral organs. The spectra of V products in RBC were independent of the initial V complex, and were best fitted by a combination of V(IV)-carbohydrate (2-hydroxyacid moieties) and/or citrate (65-85%) and V(V)-protein (15-35%) models. The presence of RBC created a more reducing environment in the plasma fraction of whole blood compared with those in isolated plasma or serum, as shown by the differences in distribution of V(IV) and V(V) species in the reaction products of A-D in these media. At physiologically relevant V concentrations (<50 μM), this role of RBC may promote the formation of V(III)-transferrin as a major V carrier in the blood plasma. The results reported herein have broad implications for the roles of RBC in the transport and speciation of metal pro-drugs that have broad applications across medicine.
dc.description.statementofresponsibilityAviva Levina, Andrew I. McLeod, Sylvia J. Gasparini, Annie Nguyen, W. G. Manori De Silva, Jade B. Aitken, Hugh H. Harris, Chris Glover, Bernt Johannessen, and Peter A. Lay
dc.identifier.citationInorganic Chemistry, 2015; 54(16):7753-7766
dc.identifier.doi10.1021/acs.inorgchem.5b00665
dc.identifier.issn0020-1669
dc.identifier.issn1520-510X
dc.identifier.orcidHarris, H. [0000-0002-3472-8628]
dc.identifier.urihttp://hdl.handle.net/2440/94159
dc.language.isoen
dc.publisherAmerican Chemical Society
dc.relation.granthttp://purl.org/au-research/grants/arc/DP0774173
dc.relation.granthttp://purl.org/au-research/grants/arc/DP0208409
dc.relation.granthttp://purl.org/au-research/grants/arc/DP0984722
dc.relation.granthttp://purl.org/au-research/grants/arc/DP1095310
dc.relation.granthttp://purl.org/au-research/grants/arc/DP130103566
dc.relation.granthttp://purl.org/au-research/grants/arc/DP0208409
dc.relation.granthttp://purl.org/au-research/grants/arc/DP0984722
dc.relation.granthttp://purl.org/au-research/grants/arc/LE0346515
dc.relation.granthttp://purl.org/au-research/grants/arc/LE0989759
dc.relation.granthttp://purl.org/au-research/grants/arc/LE110100174
dc.rights© 2015 American Chemical Society
dc.source.urihttps://doi.org/10.1021/acs.inorgchem.5b00665
dc.subjectErythrocytes
dc.subjectAnimals
dc.subjectCattle
dc.subjectRats
dc.subjectVanadium
dc.subjectOrganometallic Compounds
dc.subjectBlood Proteins
dc.subjectHypoglycemic Agents
dc.subjectBiological Transport
dc.subjectX-Ray Absorption Spectroscopy
dc.titleReactivity and speciation of anti-diabetic vanadium complexes in whole blood and its components: the important role of red blood cells
dc.typeJournal article
pubs.publication-statusPublished

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