The Iron Chelator Pyridoxal Isonicotinoyl Hydrazone Inhibits Mitochondrial Lipid Peroxidation Induced By Fe(ii)-citrate

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 μM induced full protection against 50 μM Fe(II)-citrate-induced loss of mitochondrial transmembrane potential (Δψ) 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 μM PIH (on TBARS formation and mitochondrial swelling) was greater in the presence of 20 or 50 μM Fe(II)-citrate than in the presence of 100 μM 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 2 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. © 2001 Elsevier Science B.V. All rights reserved.42813744Bhattacharya, M., Ponka, P., Hardy, P., Hanna, N., Varma, D.R., Lachapelle, P., Chemtob, S., Prevention of postasphyxia electroretinal dysfunction with a pyridoxal hydrazone (1997) Free Radical Biol. 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