Studies on the reactivity of acyl glucuronides-VII. Salicyl acyl glucuronide reactivity in vitro and covalent binding of salicylic acid to plasma protein of humans taking aspirin

Dickinson R.G., Baker P.V. and King A.R. (1994) Studies on the reactivity of acyl glucuronides-VII. Salicyl acyl glucuronide reactivity in vitro and covalent binding of salicylic acid to plasma protein of humans taking aspirin. Biochemical Pharmacology, 47 3: 469-476. doi:10.1016/0006-2952(94)90177-5


Author Dickinson R.G.
Baker P.V.
King A.R.
Title Studies on the reactivity of acyl glucuronides-VII. Salicyl acyl glucuronide reactivity in vitro and covalent binding of salicylic acid to plasma protein of humans taking aspirin
Journal name Biochemical Pharmacology   Check publisher's open access policy
ISSN 0006-2952
Publication date 1994-02-09
Sub-type Article (original research)
DOI 10.1016/0006-2952(94)90177-5
Volume 47
Issue 3
Start page 469
End page 476
Total pages 8
Subject 3004 Pharmacology
Abstract Salicyl acyl glucuronide (SAG) is a significant metabolite of salicylic acid (SA) and aspirin. We have shown that, under physiological conditions in vitro, SAG undergoes rearrangement in a manner consistent with acyl migration to its 2-, 3- and 4-O-acyl positional isomers as the predominant pathway (T 1 2 values were 1.4-1.7 hr in buffer at pH 7.4 and 37°). Incubation of SAG or a mixture of its rearrangement isomers (iso-SAG) (each at ∼50 μg SA equivalents/mL) with human serum albumin (HSA, at ∼40 mg/mL) revealed the formation of covalent adducts with the protein, with peak concentrations of 1-2 μg SA equivalents/mL. The data support a role for the rearrangement/glycation mechanism of adduct formation. Covalent adducts of SA were also detected in the plasma of humans taking aspirin (at ≥1200 mg/day), but the concentrations were low (≪100ng SA equivalents/mL). Reactivity of SAG thus provides a mechanism (though of uncertain quantitative importance) of covalent attachment of the salicyl moiety of aspirin to tissue macromolecules, which is in addition to its well-known acetylating capacity.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collection: Scopus Import
 
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