Antioxidant and prooxidant actions of gallic acid derivatives: Effect on metal-dependent oxidation of lipids and low density lipoprotein

Antioxidant and prooxidant activities of gallic acid and its alkylesters su ch as ethyl-, propyl-, butyl-, octyl- and laurylgallates were analyzed. Inc reased length of the alkyl chain in gallate esters enhanced the inhibitory effect on the iron-mediated lipid peroxidation. The concentrations of alkyl galltes required for the inhibition of the formation of thiobarbituric acid -reactive substances were dependent on the hydrophobicity of the compounds. Effectiveness of gallate compounds as antioxidants can be explained by hyd rophobic binding of the compounds to membrane lipids. Gallic acid compounds also showed a prooxidant effect by stimulating the copper-dependent oxidat ion of low density lipoprotein. The most potent prooxidant was gallic acid followed by ethyl-, propyl-, and butylgallates in this order, and octyl- an d laurylgallates did not stimulate the oxidation of low density liporotein. These prooxidant effects of gallate compounds correlated with the copper r educing activity. Addition of superoxide dismutase protected low density li poprotein from the copper-dependent oxidation by gallate compounds, indicat ing that superoxide radical formed by the cuprous ion-mediated reduction of oxygen may participate in the oxidation of low density lipoprotein. Prooxi dant action of gallate compounds may explain the cytotoxic effect of these compounds.