Apparent hydroxyl radical generation without transition metal catalysis and tyrosine nitration during oxidation of the anti-tubercular drug, isonicotinic acid hydrazide
Date
1994
Authors
Van Zyl J.M.
Van Der Walt B.J.
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Abstract
Aromatic hydroxylation and formation of thiobarbituric acid-reactive substances occurred in a mixture of isonicotinic acid hydrazide (isoniazid) and catalase. Since these reactions were stimulated by phytic acid (a potent metal chelator), rather than inhibited, transition metal-catalysed hydroxyl radical generation was not implicated. Hydroxylation also occurred with isoniazid and phytic acid in the absence of catalase, albeit to a lesser extent. The independent effects of catalase and phytic acid are related to their abilities to catalyse isoniazid oxidation. In the presence of tyrosine, both the isoniazid/phytic acid system and authentic peroxynitrite generated dityrosine. Authentic peroxynitrite, as well as a phytic acid-mediated isoniazid oxidation product, have absorbance maxima at 302 nm. The yield of this isoniazid-derived product increased with pi-I and in the presence of a superoxide-generating system. A good correlation existed between absorbance at 302 nm and aromatic hydroxylation. Acid-induced decomposition of the 302 nm absorbance in the presence of superoxide dismutase led to the formation of a product absorbing in the same region as peroxynitrite-modified superoxide dismutase (350 nm at acid pH). Catalase catalysed peroxynitrite-mediated, as well as isoniazid/phytic acid-mediated tyrosine nitration, which was accompanied by Compound II formation (ferryl-catalase) in both cases. We postulate that peroxynitrite or a similar species is formed during isoniazid oxidation.
Description
Keywords
catalase, hydroxyl radical, isoniazid, peroxynitrite, phytic acid, article, hydroxylation, priority journal, Catalase, Hydroxyl Radical, Isoniazid, Kinetics, Metals, Nitrates, Oxidation-Reduction, Spectrophotometry, Ultraviolet, Support, Non-U.S. Gov't, Thiobarbituric Acid Reactive Substances, Tyrosine
Citation
Biochemical Pharmacology
48
11
48
11