The iron chelator pyridoxal isonicotinoyl hydrazone inhibits mitochondrial lipid peroxidation induced by Fe(II)-citrate.
Eur J Pharmacol
; 428(1): 37-44, 2001 Sep 28.
Article
en En
| MEDLINE
| ID: mdl-11779035
ABSTRACT
Pyridoxal isonicotinoyl hydrazone (PIH) is able to prevent iron-mediated hydroxyl radical formation by means of iron chelation and inhibition of redox cycling of the metal. In this study, we investigated the effect of PIH on Fe(II)-citrate-mediated lipid peroxidation and damage to isolated rat liver mitochondria. Lipid peroxidation was quantified by the production of thiobarbituric acid-reactive substances (TBARS) and by antimycin A-insensitive oxygen consumption. PIH at 300 microM induced full protection against 50 microM Fe(II)-citrate-induced loss of mitochondrial transmembrane potential (deltapsi) and mitochondrial swelling. In addition, PIH prevented the Fe(II)-citrate-dependent formation of TBARS and antimycin A-insensitive oxygen consumption. The antioxidant effectiveness of 100 microM PIH (on TBARS formation and mitochondrial swelling) was greater in the presence of 20 or 50 microM Fe(II)-citrate than in the presence of 100 microM Fe(II)-citrate, suggesting that the mechanism of PIH antioxidant action is linked with its Fe(II) chelating property. Finally, PIH increased the rate of Fe(II) autoxidation by sequestering iron from the Fe(II)-citrate complex, forming a Fe(III)-PIH, complex that does not participate in Fenton-type reactions and lipid peroxidation. These results are of pharmacological relevance since PIH is a potential candidate for chelation therapy in diseases related to abnormal intracellular iron distribution and/or iron overload.
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Bases de datos:
MEDLINE
Asunto principal:
Piridoxal
/
Mitocondrias Hepáticas
/
Compuestos Férricos
/
Peroxidación de Lípido
/
Quelantes del Hierro
/
Isoniazida
/
Antioxidantes
Idioma:
En
Revista:
Eur J Pharmacol
Año:
2001
Tipo del documento:
Article
País de afiliación:
Brasil