The iron chelator pyridoxal isonicotinoyl hydrazone (PIH) protects plasmid pUC-18 DNA against *OH-mediated strand breaks.
Pyridoxal isonicotinoyl hydrazone (PIH) has previously been studied for use in iron chelation therapy in iron-overload diseases. It is an efficient in vitro antioxidant due to its Fe(III) complexing activity (Schulman, H. M., et al. Redox Report 1:373-378; 1995). Pathologies associated with iron-overload include hepatic and other cancers. Since oxidative alterations of DNA can be linked to the development of cancer, we decided to study whether PIH protects DNA against in vitro oxidative stress. We report here that pUC-18 plasmid DNA is damaged by *OH radicals generated from Fe(II) plus H2O2 or from Fe(II) plus hypoxanthine/xanthine oxidase. The DNA damage was quantified by determining the diminution of supercoiled DNA forms after oxidative attack using agar gel electrophoresis. Micromolar amounts of PIH (20-30 microM) were able to half-protect DNA from iron (1-7.5 microM)-mediated *OH formation. The antioxidant capacity of PIH was significantly higher than that of some of its analogs and desferrioxamine. PIH and some of its analogues could also inhibit the oxidative degradation of 2-deoxyribose caused by Fenton reagents. Since we observed that PIH enhances the Fe(II) autoxidation rate, measured by the ferrozine technique, PIH may limit *OH formation and consequently DNA damage by decreasing the amount of Fe(II) available to catalyze Fenton reactions.
Hermes-Lima
M
M
Departamento de Biologia Celular, Universidade de Brasilia, DF, Brazil. hermes@guarany.cpd.unb.br
Nagy
E
E
Ponka
P
P
Schulman
H M
HM
D000975:Antioxidants; D004249:DNA Damage / Q000187:drug effects*; D005296:Ferrous Compounds / Q000737:chemistry; D017665:Hydroxyl Radical / Q000378:metabolism / Q000494:pharmacology*; D019271:Hypoxanthine / Q000494:pharmacology; D007502:Iron Chelating Agents / Q000494:pharmacology*; D007538:Isoniazid / Q000031:analogs & derivatives* / Q000494:pharmacology; D010084:Oxidation-Reduction; D010957:Plasmids / Q000235:genetics*; D011730:Pyridoxal / Q000031:analogs & derivatives* / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000494:pharmacology
D000975:Antioxidants; D005296:Ferrous Compounds; D007502:Iron Chelating Agents; D019271:Hypoxanthine; D017665:Hydroxyl Radical; D011730:Pyridoxal; C021079:pyridoxal isonicotinoyl hydrazone; D014969:Xanthine Oxidase; D007538:Isoniazid