Apparent hydroxyl radical generation without transition metal catalysis and tyrosine nitration during oxidation of the anti-tubercular drug, isonicotinic acid hydrazide.
Biochem Pharmacol
; 48(11): 2033-42, 1994 Nov 29.
Article
em En
| MEDLINE
| ID: mdl-7802692
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 pH 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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tirosina
/
Radical Hidroxila
/
Isoniazida
/
Metais
Idioma:
En
Revista:
Biochem Pharmacol
Ano de publicação:
1994
Tipo de documento:
Article
País de afiliação:
África do Sul