Is homocysteine a pro-oxidant?

High plasma homocysteine concentrations have been found to be associated wi th atherosclerosis and thrombosis of arteries and deep veins. The oxidative damage mediated by hydrogen peroxide production during the metal-catalyzed oxidation of homocysteine is to date considered to be one of the major pat hophysiological. mechanisms for this association. In this work, a very sensitive and accurate method was employed to measure the effective production of H2O2 during homocysteine oxidation. Furthermore , the interaction of homocysteine with powerful oxidizing species (hypochlo rite, peroxynitrite, ferrylmyoglobin) was evaluated in order to ascertain t he putative pro-oxidant role of homocysteine. Our findings indicate that homocysteine does not produce H2O2 in a signific ant amount (1/4000 mole/mole ratio of H2O2 to homocysteine). Moreover, homo cysteine strongly inhibits the oxidation of luminol and dihydrorhodamine by hypochlorite or peroxynitrite and rapidly reduces back ferrylmyoglobin, th e oxidizing species, to metmyoglobin. All these results should, in our opinion, lead to a rethinking of the commo nly held view that homocysteine oxidation is one of the main causative mech anisms of cardiovascular damage.