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Formation of Nitroapocynin and Diapocynin in Reactions of Apocynin with Peroxynitrite/CO 2 : Implications for the use of Apocynin as a Selective Inhibitor of NADPH Oxidase System
Author(s) -
Gernapudi Ramkishore,
Babu Sainath,
Raghavame Achuthan C,
Uppu Rao M
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.lb397
Subject(s) - chemistry , apocynin , peroxynitrite , yield (engineering) , nadph oxidase , superoxide , radical , bicarbonate , inorganic chemistry , medicinal chemistry , oxidase test , nitric oxide , nuclear chemistry , organic chemistry , biochemistry , oxidative stress , enzyme , materials science , metallurgy
Peroxynitrite (PN) is an elusive oxidant formed in biological systems from the reaction of nitric oxide ( • NO) with superoxide (O 2 •– ). In bicarbonate‐rich physiological fluids, PN reacts predominantly with CO 2 forming nitrogen dioxide ( • NO 2 ) and carbonate radicals (CO 3 •– ) in yields up to 40 mol% which, in turn, react with target molecules. In the present study, we examined the reactions of PN/CO 2 with apocynin (Apo), a classical inhibitor of NADPH oxidase system with potential for treating inflammatory and degenerative conditions. At pH 7.2, Apo readily reacted in PN/CO 2 system with an over all yield of oxidation of 36 ± 2 mol% (based on the initial concentration of PN employed). About 85% of the oxidation of Apo could be accounted for by the formation nitroapocynin (NitroApo; 5.4 ± 0.2 mol%) and diapocynin (DiApo; 12.8 ± 0.7 mol%). When pH was varied between 5.76 and 8.34, the yield of NitroApo increased until pH 6.74 and then tended to decline. The yield of DiApo, on the other hand, decreased with increase in the pH. At a given pH, the yield of NitroApo but not DiApo decreased with increase in the concentration of Apo. These results are consistent with the reactions of CO 3▸ and •NO 2 with the phenol and phenolate forms of Apo and their 1‐electron oxidation product, Apo phenolate radical. The implications of Apo reaction in the PN/CO 2 system will be discussed in relation to the specificity of Apo as a probe for NADPH oxidase system and the possible metabolism of xenobitics in general by ▸NO‐derived oxidants.