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A reassessment of the peroxynitrite scavenging activity of uric acid.
Ann N Y Acad Sci. 2002 May; 962:242-59.AN

Abstract

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 alpha(1)-antiproteinase (alpha(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 alpha(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.

Authors+Show Affiliations

Department of Biochemistry, Faculty of Medicine, National University of Singapore, Singapore.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12076979

Citation

Whiteman, M, et al. "A Reassessment of the Peroxynitrite Scavenging Activity of Uric Acid." Annals of the New York Academy of Sciences, vol. 962, 2002, pp. 242-59.
Whiteman M, Ketsawatsakul U, Halliwell B. A reassessment of the peroxynitrite scavenging activity of uric acid. Ann N Y Acad Sci. 2002;962:242-59.
Whiteman, M., Ketsawatsakul, U., & Halliwell, B. (2002). A reassessment of the peroxynitrite scavenging activity of uric acid. Annals of the New York Academy of Sciences, 962, 242-59.
Whiteman M, Ketsawatsakul U, Halliwell B. A Reassessment of the Peroxynitrite Scavenging Activity of Uric Acid. Ann N Y Acad Sci. 2002;962:242-59. PubMed PMID: 12076979.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A reassessment of the peroxynitrite scavenging activity of uric acid. AU - Whiteman,M, AU - Ketsawatsakul,U, AU - Halliwell,B, PY - 2002/6/22/pubmed PY - 2002/7/27/medline PY - 2002/6/22/entrez SP - 242 EP - 59 JF - Annals of the New York Academy of Sciences JO - Ann N Y Acad Sci VL - 962 N2 - 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 alpha(1)-antiproteinase (alpha(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 alpha(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. SN - 0077-8923 UR - https://www.unboundmedicine.com/medline/citation/12076979/A_reassessment_of_the_peroxynitrite_scavenging_activity_of_uric_acid_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0077-8923&date=2002&volume=962&spage=242 DB - PRIME DP - Unbound Medicine ER -