Abstract
Paraoxonase 1 (PON 1) is an enzyme that is promiscuous in its ability to hydrolyze
various types of substrates. It hydrolyzes aryl esters, phosphate esters, lactones,
and reduces lipid peroxides to hydroxides. Aspirin is an aryl ester with a short plasma
half life. We hypothesized that aspirin would be effectively hydrolyzed by PON 1 and
many of its anti-atherogenic effects, at least in part, could be accounted for by
its antioxidant product, salicylic acid. In this study, we determined the ability
of human plasma and PON 1-rich HDL to hydrolyze acetyl ester of salicylic acid (aspirin).
The ability of aspirin to compete for the hydrolysis of paraoxon and p-nitrophenylacetate was determined. In addition, nitrated aspirin was synthesized
and tested directly for hydrolysis. Aspirin competed for the hydrolysis of paraoxon
and p-nitrophenylacetate by HDL in a dose-dependent manner. Human plasma and HDL were also
able to hydrolyze nitroaspirin and aspirin and release nitrosalicylic acid and salicylic
acid, respectively. These findings suggest that salicylic acid might be generated
in the plasma from aspirin. The ability of long-term treatment with aspirin to retard
atherosclerosis might be dependent on the generation of free salicylic acid, a scavenger
of free radicals.
Keywords
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Article info
Publication history
Published online: June 22, 2006
Accepted:
May 12,
2006
Received in revised form:
March 25,
2006
Received:
January 12,
2006
Identification
Copyright
© 2006 Elsevier Ireland Ltd. Published by Elsevier Inc. All rights reserved.
