Antioxidant and anti-inflammatory like properties of benzoic acid analogs on the oxidant response of neutrophils: structure/redox potential relationship study.

We investigated the antioxidant capacity of phenolic acid derivatives by measuring their capacity to prevent ABTS oxidation and evaluating their anti-inflammatory like-properties on the oxidant response of neutrophils, especially on superoxide anion production and the activity of myeloperoxidase (MPO), an oxidant enzyme present and released by the primary granules of neutrophils.
The superoxide anion production by PMA-stimulated neutrophils was measured by lucigenin-enhanced chimiluminescence (CL) and the activity of MPO by SIEFED to study the potential interaction of a molecule with the enzyme without interferences due to medium. The antioxidant and anti-inflammatory activities of the phenolic compounds were correlated to their redox potentials measured by voltammetry method, and discussed in relation to their molecular structure.
The ability of the phenolic molecules to decrease ABTS oxidation and CL production was inversely correlated to their redox potential increasing as follows: propyl gallate > gallic acid > caffeic acid > 3,4-dihydroxybenzoic acid > ferulic acid > syringic acid > 2,6-dihydroxybenzoic acid > salicylic acid > benzoic acid. The number of hydroxyl groups (3) and their position (catechol) were essential for the efficacy of the molecules as stoichiometric antioxidants or scavengers. On MPO activity, the inhibitory capacity of the molecules was not really correlated with their redox potential and increased as follows: gallic acid > caffeic acid > 2,6-dihydroxybenzoic acid > propyl gallate > ferulic acid = syringic acid > 3,4-dihydroxybenzoic acid = salicylic acid > benzoic acid. The number of OH groups and the elongation of the carboxyl group were essential for the inhibition of MPO activity, probably by facilitating the interaction with the MPO active site or structure. The redox potential measurement seems to be a good technique to select stoichiometric antioxidants, but not anti-catalytic ones.