Glycation of human serum albumin by acylglucuronides of nonsteroidal anti-inflammatory drugs of the series of phenylpropionates.
The covalent binding to human serum albumin (HSA), of acylglucuronides from carboxylic nonsteroidal anti-inflammatory drugs (NSAIDs) was investigated. The adduct formation was followed and quantitated by HPLC and by radiometric detection. Three types of albumin adducts were evidenced. The acylglucuronide or the drug itself was bound to 0.2 up to 9% of the albumin molecules, depending on the drug, whereas the majority of adducts (23-49% of albumin molecules) retained the glucuronic acid moiety. The possible involvement of specific Lys located in site I of albumin in the formation of these main adducts was demonstrated, using a series of HSA whose specific Lys residues have been modified chemically. This study shows that acylglucuronides from NSAIDs can significantly contribute to the glycation of proteins, such as albumin.
Georges
H
H
Physiopathologie et Pharmacologie Articulaires, UMR 7561 CNRS-UHP Nancy 1, France.
Jarecki
I
I
Netter
P
P
Magdalou
J
J
Lapicque
F
F
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism*; D005965:Glucuronates / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D008239:Lysine / Q000378:metabolism; D012709:Serum Albumin / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D005965:Glucuronates; D012709:Serum Albumin; D008239:Lysine