title: Impaired drug-binding capacities of in vitro and in vivo glycated albumin.
abstract: 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.
authors.affiliation: Groupe d'Etude sur l'Inflammation Chronique et l'Obésité, Structure fédérative Environnement Biodiversité Santé-FED4126, Université de La Réunion, Plateforme CYROI, 15, avenue René Cassin - BP 7151, 97715 Saint Denis Messag Cedex 09, La Réunion, France.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Baraka-Vidot
authors.forename: Alexis
authors.initials: A
authors.lastname: Guerin-Dubourg
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Bourdon
authors.forename: Philippe
authors.initials: P
authors.lastname: Rondeau
mesh_terms: D000328:Adult; D005260:Female; D017127:Glycation End Products, Advanced; D006801:Humans; D007660:Ketoprofen / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism*; D014859:Warfarin / Q000378:metabolism*; D000093423:Glycated Serum Albumin
chemical_list: D017127:Glycation End Products, Advanced; D012709:Serum Albumin; D014859:Warfarin; D007660:Ketoprofen; D000093423:Glycated Serum Albumin