Department of Biochemistry, Faculty of Medicine, National University of Singapore, Singapore
Address for correspondence: Department of Biochemistry, Faculty of Medicine, National University of Singapore, 10 Kent Ridge Crescent, Singapore 119260. Voice: +65-874-8891; fax: +65-779-1453.
bchwml{at}nus.edu.sg
Ann. N.Y. Acad. Sci. 962: 242-259 (2002).
Peroxynitrite is implicated in numerous human diseases. Hence,
there is considerable interest in potential therapeutic peroxynitrite
scavengers. It has been claimed that uric acid is a powerful
peroxynitrite scavenger. We previously observed that uric acid
is a powerful inhibitor of tyrosine nitration induced by peroxynitrite,
but fails to prevent
1-antiproteinase (
1-AP) inactivation induced
by peroxynitrite. However, the reactivity of peroxynitrite is
significantly modified by bicarbonate and this has not been
considered in evaluating the scavenging activity of uric acid
and other endogenous antioxidant compounds. In the presence
of bicarbonate (25 mM), the ability of uric acid, ascorbate,
Trolox, and GSH to inhibit peroxynitrite-mediated tyrosine and
guanine nitration is decreased. Protection against peroxynitrite-mediated
1-AP inactivation is also decreased by ascorbate, Trolox, and
GSH, but it is enhanced by uric acid. Bicarbonate also inhibits
the ability of these compounds to prevent peroxynitrite-mediated
ABTS radical cation formation. However, the abilities of these
antioxidants to prevent peroxynitrite-mediated bleaching of
pyrogallol red are enhanced by bicarbonate. These results show
that physiologic concentrations of bicarbonate substantially
modify the ability of uric acid to prevent peroxynitrite-mediated
reactions. This study highlights the need to use several different
assays in the presence of physiologically relevant concentrations
of bicarbonate when assessing compounds for peroxynitrite scavenging,
in order to avoid misleading results.
• superoxide.
