Genoprotective Effect of Some Flavonoids against Genotoxic Damage Induced by X-rays In Vivo: Relationship between Structure and Activity

Abstract

Flavonoids constitute a group of polyphenolic compounds characterized by a common gamma-benzo- pyrone structure considered in numerous biological systems to possess antioxidant capacity. Among the different applications of flavonoids, its genoprotective capacity against damage induced by ionizing radiation stands out, which has been related to antioxidant activity and its chemical structure. In this study, we determined the frequency of appearance of micronucleus in vivo by means of the micronucleus assay. This was conducted in mice treated with different flavonoids before and after exposure to 470 mGy X-rays; thereafter, their bone marrow polychromatophilic erythrocytes were evaluated to establish the structural factors enhancing the observed genoprotective effect. Our results in vivo show that the presence of a monomeric flavan-3-ol type structure, with absence of carbonyl group in position C4 of ring C, absence of conjugation between the carbons bearing the C2 = C3 double bond and the said ring, presence of a catechol group in ring B and characteristic hydroxylation in positions 5 and 7 of ring A are the structural characteristics that determine the highest degree of genoprotection. Additionally, a certain degree of polymerization of this flavonoid monomer, but maintaining significant levels of monomers and dimers, contributes to increasing the degree of genoprotection in the animals studied at both times of their administration (before and after exposure to X-rays).

Nuclear and Radiological Emergencies: Biological Effects, Countermeasures and Biodosimetry

“…Thereby, differences in ROS scavenging potential can be attributed to the different functional groups attached to the main nucleus [ 100 ]. Intercalation in DNA double helices induces stabilization and condensation of DNA structures making them less susceptible to free radicals’ attack [ 100 ], reducing genotoxic damage induced by IR [ 101 ]. Xanthine oxidase and lipoxygenase are inhibited by many polyphenols, thus reducing the generation of free radicals.…”

Paradoxical Radiosensitizing Effect of Carnosic Acid on B16F10 Metastatic Melanoma Cells: A New Treatment Strategy

“…We used these three different cytogenetic assays in a complementary way to confirm the genotoxic capacity of X-rays by determining the frequency of appearance of MN in irradiated human lymphocytes and in animals exposed to ionizing radiation. On the other hand, a reduction of this MN frequency confirms the protective capacity (antigenotoxic effect) of CA against damage induced by ionizing radiation [38][39][40][41]. In addition, it was possible to determine the in vivo and in vitro genotoxic effects of irradiated serum from recipient animals and irradiated medium obtained from irradiated cultures cells, respectively, in order to characterize the RIBE [32].…”

Differential Radiomodulating Action of Olea europaea L. cv. Caiazzana Leaf Extract on Human Normal and Cancer Cells: A Joint Chemical and Radiobiological Approach

“…Our data showing an OLC-mediated reduction in radiation-induced genotoxicity, expressed in the form of MN scored in normal BN cells ( Figure 6 ), are in keeping with similar findings that have been scantly reported over a long time on the radioprotection afforded by polyphenols to irradiated cellular DNA using the same endpoint. Thus, while, almost twenty years ago, Greenrod and Fenech [ 70 ] had assessed the impact of several wine-derived polyphenols on human lymphocytes irradiated in vitro by the CBMN assay reporting an anti-genotoxic action, Alcaraz et al [ 71 ] very recently reported on the radioprotective effect by flavonoids in mice whole-body irradiated with 0.5 Gy of γ-radiation assessed by MN formation in polychromatic erythrocytes. More specifically, another recent work by Amani et al [ 72 ] found that 100 mM of oleuropein afforded protection from apoptosis, clastogenicity, and genotoxicity, with the latter measured by MN occurrence, in human cultured lymphocytes exposed to a single dose of 2 Gy of γ-rays.…”

“…Radiation would add to such a higher “background” oxidative stress in cancer cells. As suggested by Alcaraz et al [ 71 ], under certain conditions depending, among other factors, on the number and positions of hydroxyl groups, polyphenolic compounds through the chelation of chromosome-associated metal ion Cu 2+ can switch from an anti-oxidant to a pro-oxidant activity, a mechanism already postulated to explain flavonoid-mediated DNA damage [ 77 ]. Thus, it is possible that, in normal cells, the additional level of ROS produced by radiation can be dealt with effectively by the anti-oxidant scavenging ability of the oleuropein-rich OLC at the concentration used in this study, whereas the peculiar redox status of cancer cells combined with the mentioned properties of oleuropein and the additional radiation-induced ROS could reverse the same amount of OLC to an effective pro-oxidant agent.…”