title: In vitro antioxidant properties of the iron chelator pyridoxal isonicotinoyl hydrazone and some of its analogs.
abstract: Since there are several problems with desferrioxamine (DFO) therapy, pyridoxal isonicotinoyl hydrazone (PIH) has been studied for more than 10 years as a promising new candidate for iron chelation therapy in iron-overload diseases. Iron chelation could also be helpful for experimental treatment of several other pathologies including rheumatoid arthritis and heart ischemia/reperfusion, due to the generation of oxyradicals and lipid peroxidation mediated by delocalized iron. We demonstrate here that sub-millimolar levels of PIH can inhibit the Fe(III)-EDTA/ascorbate-mediated formation of hydroxyl-like radicals as tested by the release of ethylene from 2-keto-4-methylthiobutyric acid (KMB assay) and the formation of malonaldehyde from 2-deoxyribose damage. PIH could also decrease the rates of Fe(III)-EDTA-mediated oxidation of ascorbate and block the peroxidation of liposomes of rat brain phospholipids induced by ferrous iron-EDTA. In all cases the in vitro antioxidant effectiveness of PIH was comparable to its analogs-including salicylaldehyde isonicotinoyl hydrazone-and to DFO. We conclude that PIH and its analogs are effective new candidates against iron-mediated oxidative stress for use in experimental medicine.
authors.affiliation: a Lady Davis Institute for Medical Research, Jewish General Hospital , Montreal , Canada.
authors.forename: H M
authors.initials: HM
authors.lastname: Schulman
authors.affiliation: a Lady Davis Institute for Medical Research, Jewish General Hospital , Montreal , Canada.|b Departamento de Bioquimica Medica , Universidade Federal do Rio de Janeiro , Rio de Janeiro , Brazil.
authors.forename: M
authors.initials: M
authors.lastname: Hermes-Lima
authors.affiliation: a Lady Davis Institute for Medical Research, Jewish General Hospital , Montreal , Canada.
authors.forename: E M
authors.initials: EM
authors.lastname: Wang
authors.affiliation: a Lady Davis Institute for Medical Research, Jewish General Hospital , Montreal , Canada.|c Departments of Physiology and Medicine , McGill University , Montreal , Canada.
authors.forename: P
authors.initials: P
authors.lastname: Ponka