Haiying Fu

Free radical scavenging reactions and antioxidant activities of silybin: Mechanistic aspects and pulse radiolytic studies

Silybin (extracted from Silybum marianum) is the major active constituent of silymarin which possesses a wide range of medicinal properties. These properties may be, in part, due to the potent scavenging capacity of oxidizing free radicals. In this context, scavenging radicals (hydroxyl, azide, dibromide anion radicals, nitrite, carbonate, etc.) of silybin have been studied to understand the mechanistic aspects of its action against free radicals. The transients produced in these reactions have been assigned and the rate constants have been measured by pulse radiolysis techniques. Reduction potential determined both by cyclic voltammetry gave a value 0.62±0.02 V vs NHE at pH 9. Quantum chemical calculations have been performed to further confirm the different activities of individual hydroxyl groups with the difference of heat of formation. Moreover, silybin also protected plasmid pUC18 DNA from soft X-ray radiation which induced strand breaks. These results are expected to be helpful for a better understanding of the anti-oxidative properties of silybin.

Protective effects of silybin and analogues against X-ray radiation-induced damage.

Silybin (SLB) and similar analogues, namely, hesperetin (HESP), naringenin (NAN) and naringin (NAR), are believed to be active constituents of natural flavonoids that have been reported as chemopreventive agents for certain cancers. Moreover, SLB and analogues have been determined to fast repair DNA bases from oxidative damage by pulse radiolysis techniques. The present study was designed to evaluate the protective effects of SLB and analogues on soft X-ray-induced damage to plasmid DNA in vitro. The DNA damage was determined by agarose gel electrophoresis. SLB and analogues were found to protect DNA from radiation damage at micromolar concentrations. Among the compounds tested, HESP and SLB were the most effective in preventing X-ray-induced formation of DNA single-strand breaks (SSB). A comparison of these results with other experiments showed that the ability of SLB and analogues to inhibit DNA damage in vitro correlated with the ability of the compounds to scavenge free radicals. Our work revealed that natural flavonoids, SLB and analogues may be used as potent radioprotectors against radiation damage.

Temperature Dependent Absorption Spectra of Br−, Br2•−, and Br3− in Aqueous Solutions

The absorption spectra of Br(2)(•-) and Br(3)(-) in aqueous solutions are investigated by pulse radiolysis techniques from room temperature to 380 and 350 °C, respectively. Br(2)(•-) can be observed even in supercritical conditions, showing that this species could be used as a probe in pulse radiolysis at high temperature and even under supercritical conditions. The weak temperature effect on the absorption spectra of Br(2)(•-) and Br(3)(-) is because, in these two systems, the transition occurs between two valence states; for example, for Br(2)(-) we have (2)Σ(u) → (2)Σ(g) transition. These valence transitions involve no diffuse final state. However, the absorption band of Br(-) undergoes an important red shift to longer wavelengths. We performed classical dynamics of hydrated Br(-) system at 20 and 300 °C under pressure of 25 MPa. The radial distribution functions (rdfs) show that the strong temperature increase (from 20 to 300 °C) does not change the radius of the solvent first shell. On the other hand, it shifts dramatically (by 1 Å) the second maximum of the Br-O rdf and introduces much disorder. This shows that the first water shell is strongly bound to the anion whatever the temperature. The first two water shells form a cavity of a roughly spherical shape around the anion. By TDDFT method, we calculated the absorption spectra of hydrated Br(-) at two temperatures and we compared the results with the experimental data.

Pulse Radiolysis Studies on the Temperature-Dependent Spectrum and the Time-Dependent Yield of Solvated Electron in Propane-1,2,3-triol

With a revisit of the absorption coefficient of the solvated electron in propane-1,2,3-triol, the temperature-dependent behavior of the absorption spectrum of solvated electron was studied from room temperature to 573 K by pulse radiolysis techniques. The change in the absorption spectrum of solvated electron in propane-1,2,3-triol observed by cooling down from a high temperature to 333 K is compared with that occurring during the electron solvation process at 333 K. The effect of the specific molecular structure of propane-1,2,3-triol compared to other alcohols is discussed.

Chemical repair activity of free radical scavenger edaravone: reduction reactions with dGMP hydroxyl radical adducts and suppression of base lesions and AP sites on irradiated plasmid DNA

Reactions of edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one) with deoxyguanosine monophosphate (dGMP) hydroxyl radical adducts were investigated by pulse radiolysis technique. Edaravone was found to reduce the dGMP hydroxyl radical adducts through electron transfer reactions. The rate constants of the reactions were greater than 4 × 108 dm3 mol−1 s−1 and similar to those of the reactions of ascorbic acid, which is a representative antioxidant. Yields of single-strand breaks, base lesions, and abasic sites produced in pUC18 plasmid DNA by gamma ray irradiation in the presence of low concentrations (10–1000 μmol dm−3) of edaravone were also quantified, and the chemical repair activity of edaravone was estimated by a method recently developed by the authors. By comparing suppression efficiencies to the induction of each DNA lesion, it was found that base lesions and abasic sites were suppressed by the chemical repair activity of edaravone, although the suppression of single-strand breaks was not very effective. This phenomenon was attributed to the chemical repair activity of edaravone toward base lesions and abasic sites. However, the chemical repair activity of edaravone for base lesions was lower than that of ascorbic acid.