albumin - publications

Predict more albumin - ligand interactions now!

1. Biochimie. 2012 May 21. [Epub ahead of print]

Impaired drug-binding capacities of in vitro and in vivo glycated albumin.

Baraka-Vidot J, Guerin-Dubourg A, Bourdon E, Rondeau P.

Groupe d'Etude sur l'Inflammation Chronique et l'Obésité (GEICO), Structure
fédérative Environnement Biodiversité Santé- FED4126, Université de La Réunion,
Plateforme CYROI, Saint Denis de La Réunion, France.

Albumin, the major circulating protein in blood, can undergo increased glycation
in diabetes. One of the main properties of this plasma protein is its strong
affinity to bind many therapeutic drugs, including warfarin and ketoprofen. In
this study, we investigated whether or not there were any significant changes
related to in vitro or in vivo glycation in the structural properties and the
binding of human albumin to both therapeutic drugs. Structural parameters,
including redox state and ketoamine contents of in vitro and in vivo glycated
purified albumins, were investigated in parallel with their affinity for warfarin
and ketoprofen. High-performance liquid chromatography was used to determine the
free drug concentrations and dissociation constants according to the Scatchard
method. An alternative method based on fluorescence spectroscopy was also used to
assess drug-binding properties. Oxidation and glycation levels were found to be
enhanced in albumin purified from diabetic patients or glycated with glucose or
methylglyoxal, after determination of their ketoamine, free thiol, amino group
and carbonyl contents. In parallel, significant impairments in the binding
affinity of in vitro and in vivo glycated albumin, as indicated by the higher
dissociation constant values and confirmed by higher free drug fractions, were
observed. To a lesser extent, this alteration also significantly affected
diabetic albumin affinity, indicated by a lower static quenching in fluorescence
spectroscopy. This work provides useful information supporting in vivo diabetic
albumin could be the best model of glycation for monitoring diabetic
physiopathology and should be valuable to know if glycation of albumin could
contribute to variability in drugs response during diabetes.

Copyright © 2012. Published by Elsevier Masson SAS.

PMID: 22627382 [PubMed - as supplied by publisher]