IN-VITRO ANTIOXIDANT PROPERTIES OF THE IRON CHELATOR PYRIDOXAL ISONICOTINOYL HYDRAZONE AND SOME OF ITS ANALOGS

Since there are several problems with desferrioxamine (DFO) therapy, p yridoxal isonicotinoyl hydrazone (PIH) has been studied for more than 10 years as a promising new candidate for iron chelation therapy in ir on-overload diseases, Iron chelation could also be helpful for experim ental treatment of several other pathologies including rheumatoid arth ritis and heart ischemia/reperfusion, due to the generation of oxyradi cals and lipid peroxidation mediated by delocalized iron. We demonstra te here that sub-millimolar levels of PIH can inhibit the Fe(III)-EDTA /ascorbate-mediated formation of hydroxyl-like radicals as tested by t he release of ethylene from 2-keto-4-methylthiobutyric acid (KMB assay ) and the formation of malonaldehyde from 2-deoxyribose damage, PIH co uld also decrease the rates of Fe(III)-EDTA-mediated oxidation of asco rbate and block the peroxidation of liposomes of rat brain phospholipi ds induced by ferrous iron-EDTA. In all cases the in vitro antioxidant effectiveness of PIH was comparable to its analogs - including salicy laldehyde isonicotinoyl hydrazone - and to DFO, We conclude that PIH a nd its analogs are effective new candidates against iron-mediated oxid ative stress for use in experimental medicine.