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 this reaction by plant‐derived antioxidants have been investigated. Peroxynitrite promoted the oxidation of dopamine to 6‐hydroxyindole‐5‐one as characterised by HPLC and photodiode array spectra, akin to the products of the tyrosinase‐dopamine reaction, but no evidence of dopamine nitration was obtained. Although peroxynitrite did not cause nitration of dopamine in vitro, the catecholamine is capable of inhibiting the formation of 3‐nitrotyrosine from peroxynitrite‐mediated nitration of tyrosine. The plant‐derived phenolic compounds, caffeic acid and catechin, inhibited peroxynitrite‐mediated oxidation 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 antioxidant effect of caffeic acid and catechin was comparable to that of the endogenous antioxidant, glutathione. In contrast, the structurally related monohydroxylated hydroxycinnamates, p‐coumaric acid and ferulic acid, which inhibit tyrosine nitration through a mechanism of competitive nitration, did not inhibit peroxynitrite‐induced dopamine oxidation. The findings of the present study suggest that certain plant‐derived phenolics can inhibit dopamine oxidation.