A hypothesis for the in vivo antioxidant action of salicyclic acid

This paper presents a new hypothesis for the physiological antioxidant action of salicylate, Current theories have focused on the radical scavenging nature of salicylate. This explanation may have limitations because it is unlikely that salicylate reaches the necessary concentrations to effectively prevent damage to cell components, We propose that salicylic acid decreases the flux of hydroxyl radicals through chelation, which causes a redox deactivation mechanism of iron Fenton reaction centers, This is due to voltammetric results which indicate that the iron-salicylate complex does not have the thermodynamic driving force to act as an effective Fenton reagent necessary for the production of damaging oxygen-containing radicals. Furthermore, despite the more facile thermodynamics associated with Fenton-type processes at acidic pH values, the complex maintains Fenton inactivity due to a pH-sensitive redox potential shift that follows as E(Fe[Sal]) = 0.793 - (0.059 pH). This is important since inflammation sites are acidic relative to healthy tissue, This redox potential shift is unique to salicylates when compared with other common iron chelation agents such as EDTA, Further evidence for the lack of Fenton-type reactivity of the iron-salicylate complex is offered in the form of oxidation studies of calf thymus (CT) DNA by hydrogen peroxide, Salicylate prevents the iron-catalyzed oxidation of CT-DNA strands as indicated by the detection of the constituent bases by HPLC, However, salicylates were not able to prevent the copper-catalyzed oxidation of CT-DNA, These results are predicted by the cyclic voltammetry of copper-salicylate, which confirms that it is an effective Fenton-type catalyst, further adding to the proof that salicylate acts by redox deactivation of iron, not by hydroxyl radical scavenging, Finally, the iron-salicylate e.m.f. suggests that it may also act as a superoxide dismutase, which indicates another possible important antioxidant feature.