ANTIOXIDANT ACTION OF RESVERATROL IN THE PREVENTION OF GUANINE ONE-ELECTRON OXIDATION

NEYRA RECKY, JAEL R.; GASPAR TOSATO, MAIRA; SERRANO, MARIANA P; THOMAS, ANDRÉS HÉCTOR; DANTOLA, MARIA LAURA; LORENTE, CAROLINA

Barcelona

Congreso; World Congress on Light and Life (17th Congress of the International Union of Photobiology and 18th Congress of the European Society for Photobiology); 2019

International Union of Photobiology and the European Society for Photobiology

IntroductionDuring the last years, the interest in Resveratrol (3,4´,5,-trihydroxystilbene, RSV) has increased due to the evidencesfound of its antioxidant action protecting biomolecules and cells from oxidative damage and it has been furtherexacerbated by the natural presence of RSV in some fruits and derivatives, especially in red wine.1 2?-Deoxyguanosine5?-monophosphate (dGMP) is an essential constituent of DNA, and after one-electron oxidation, is modified causingDNA mutations. We evaluated the participation of RSV antioxidant action after one-electron oxidation of dGMP.MethodsKinetic analysis (HPLC-UV, UPLC-MS) during steady-state irradiation (Rayonet 3500 RPR lamp) and laser flashphotolysis experiments (LP980, Edinburgh).Results and DiscussionThe obtained results clearly demonstrate that RSV is an efficient protector of dGMP during oxidation photosensitizedby pterin. (Ptr). Under UV-A radiation, dGMP reacts with triplet excited state of the photosensitizer (3Ptr*) to yield dGMPradical cation (dGMP?+/dGMP(-H)?), which in the absence of RSV and in the presence of O2 undergoes oxidation.2 Inthis work we confirmed that RSV reacts with both 3Ptr* and dGMP(-H)?, with diffusion-controlled limit behavior (k3Ptr*= 4.94x109 M-1s-1 and kdGMP(-H)? = 1.2x109 M-1s-1, respectively). However, due to the different lifetimes values of theinvolved species, i.e. dGMP(-H)? (>100 ms) and 3Ptr* (~6 ms), at low concentration of RSV, the antioxidant reactssignificantly only with dGMP(-H)?, recovering the nucleotide and preventing its further oxidation. As RSV is a sacrificialmolecule, after reaction with dGMP(-H)?, RSV radicals formed are latter oxidized, losing the antioxidant capacity.RSV is recognized as a scavenger of Reactive Oxygen Species (ROS). During Ptr-photosensitized reactions, O2?- isformed and, in consequence H2O2 is detected in the solutions as a product. The addition of RSV does not affect thefinal H2O2 concentration, suggesting that RSV does not reacts with O2?- in the experimental conditions used. Moreover,the corresponding bimolecular rate constant (kH2O2) for the reaction between RSV and H2O2 was evaluated, and avalue of 1.16 (± 0.07) M-1s-1 was obtained. This latter result discards any reaction between RSV and H2O2 in thecurrent experimental conditions.ConclusionsConsidering the results presented here, we demonstrate that RSV is an efficient inhibitor of dGMP oxidation duringone-electron oxidation. The antioxidant mechanism involves the reaction between RSV and the nucleotide neutralradical, dGMP(-H)?, to recover the native nucleotide and prevent its permanent damage, which is the main causesof carcinogenic lesions initiation. In the absence of RSV, and after one-electron oxidation, dGMP is irremediablyoxidized, and if the damage occurs in dGMP located in DNA molecules, the consequences can be as serious asmutations and subsequent carcinogenic lesions.Continued