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Type: Artigo de periódico
Title: The iron chelator pyridoxal isonicotinoyl hydrazone inhibits mitochondrial lipid peroxidation induced by Fe(II) -citrate
Author: Santos, NCF
Castilho, RF
Meinicke, AR
Hermes-Lima, M
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 muM induced full protection against 50 muM Fe(II)-citrate-induced loss of mitochondrial transmembrane potential (Delta psi) 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 muM PIH (on TBARS formation and mitochondrial swelling) was greater in the presence of 20 or 50 muM Fe(II)-citrate than in the presence of 100 muM 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(Il)-citrate complex, forming a Fe(III)-PIH2 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. (C) 2001 Elsevier Science B.V. All rights reserved.
Subject: free radical
iron chelator
lipid peroxidation
oxidative stress
pyridoxal isonicotinoyl hydrazone
Country: Holanda
Editor: Elsevier Science Bv
Citation: European Journal Of Pharmacology. Elsevier Science Bv, v. 428, n. 1, n. 37, n. 44, 2001.
Rights: fechado
Identifier DOI: 10.1016/S0014-2999(01)01291-2
Date Issue: 2001
Appears in Collections:Unicamp - Artigos e Outros Documentos

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