A mechanistic study of the effects of antioxidants on the formation of malondialdehyde-like products in the reaction of hydroxyl radicals with deoxyribose

The reactions of OH radicals with deoxyribose, DR, form five different DR* radicals, only one of which is transformed into malondialdehyde (MDA)-like products. The radiolytic yield of the MDA-like products increases with the increase in the DR concentration indicating that some of the initially formed "unproductive" radicals react with DR to form the "productive" radicals. The yield of the MDA-like products also increases with the dose rate delivered to the solution suggesting that the formation of the MDA-like products involves the reaction of the "productive" radicals with a radical. The addition of ascorbate, AH^-, to the solution decreases the yield of the MDA-like products as ex-pected from the relative rates of the reaction of DR and AH^- with 'OH radicals. On the other hand the addition of the exogenous thiol, Ν-acetylcysteine (NAC), to the solutions decreases the yield of the MDA-like products considerably more than expected from the rate constants of the reaction with OH radicals. The addition of the endogenous thiol, glutathione (GSH), to the solutions affects the yield of the MDAlike products at low concentration less than expected and at "high" concentrations more than expected from the rate constant of the reaction. Addition of low concentration of AH ^- to solutions containing GSH increases considerably its antioxidant activity whereas addition of small concentrations of AH^- to solutions containing NAC has no effect on its antioxidant activity. The results point out that the DR* radicals react differently with NAC and GSH and that the GS* and NAC radicals react differently with DR, the GS* radical being considerably more active than the NAC radical. Thus it has to be concluded that the relative activity of antioxidants depends also on the rate constants of many secondary reactions and on the concentrations of all the solutes present in the system.