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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Identification of urate hydroperoxide in neutrophils: A novel pro-oxidant generated in inflammatory conditions

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Silva, Railmara P. [1] ; Carvalho, Larissa A. C. [1] ; Patricio, Eliziane S. [1] ; Bonifacio, Joao P. P. [1] ; Chaves-Filho, Adriano B. [1] ; Miyamoto, Sayuri [1] ; Meotti, Flavia C. [1]
Total Authors: 7
[1] Univ Sao Paulo, Inst Quim IQUSP, Dept Bioquim, Sao Paulo, SP - Brazil
Total Affiliations: 1
Document type: Journal article
Source: Free Radical Biology and Medicine; v. 126, p. 177-186, OCT 2018.
Web of Science Citations: 0

Uric acid is the final product of purine metabolism in humans and is considered to be quantitatively the main antioxidant in plasma. In vitro studies showed that the oxidation of uric acid by peroxidases, in presence of superoxide, generates urate free radical and urate hydroperoxide. Urate hydroperoxide is a strong oxidant and might be a relevant intermediate in inflammatory conditions. However, the identification of urate hydroperoxide in cells and biological samples has been a challenge due to its high reactivity. By using mass spectrometry, we undoubtedly demonstrated the formation of urate hydroperoxide and its corresponding alcohol, hydroxyisourate during the respiratory burst in peripheral blood neutrophils and in human leukemic cells differentiated in neutrophils (dHL-60). The respiratory burst was induced by phorbol myristate acetate (PMA) and greatly increased oxygen consumption and superoxide production. Both oxygen consumption and superoxide production were further augmented by incubation with uric acid. Conversely, uric acid significantly decreased the levels of HOCl, probably because of the competition with chloride by the catalysis of myeloperoxidase. In spite of the decrease in HOCl, the overall oxidative status, measured by GSH/GSSG ratio, was augmented in the presence of uric acid. In summary, the present results support the formation of urate hydroperoxide, a novel oxidant in neutrophils oxidative burst. Urate hydroperoxide is a strong oxidant and alters the redox balance toward a prooxidative environment. The production of urate hydroperoxide in inflammatory conditions could explain, at least in part, the harmful effect associated to uric acid. (AU)

FAPESP's process: 11/18106-4 - Oxidation of uric acid by myeloperoxidase in inflammatory processes and the implications for cardiovascular disease
Grantee:Flavia Carla Meotti
Support type: Research Grants - Young Investigators Grants
FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
Grantee:Ohara Augusto
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC