Inhibition of peroxynitrite-mediated oxidation of dopamine by flavonoid and phenolic antioxidants and their structural relationships

The interaction between peroxynitrite and dopamine and the inhibition of th is reaction by plant-derived antioxidants have been investigated. Peroxynit rite promoted the oxidation of dopamine to 6-hydroxyindole-5-one as charact erised by HPLC and photodiode array spectra, akin to the products of the ty rosinase-dopamine reaction, but no evidence of dopamine nitration was obtai ned. Although peroxynitrite did not cause nitration of dopamine in vitro, t he catecholamine is capable of inhibiting the formation of 3-nitrotyrosine from peroxynitrite-mediated nitration of tyrosine. The plant-derived phenol ic compounds, caffeic acid and catechin, inhibited peroxynitrite-mediated o xidation of dopamine. This effect is attributed to the ability of catechol- containing antioxidants to reduce peroxynitrite through electron donation, resulting in their oxidation to the corresponding o-quinones. The antioxida nt effect of caffeic acid and catechin was comparable to that of the endoge nous antioxidant, glutathione. In contrast, the structurally related monohy droxylated hydroxycinnamates, p-coumaric acid and ferulic acid, which inhib it tyrosine nitration through a mechanism of competitive nitration, did not inhibit peroxynitrite-induced dopamine oxidation. The findings of the pres ent study suggest that certain plant-derived phenolics can inhibit dopamine oxidation.