Design and evaluation of a novel flavonoid-based radioprotective agent utilizing monoglucosyl rutin. (24th January 2018)

• Record Type: Journal Article
• Authors: Aizawa, Yasushi; Sunada, Shigeaki; Hirakawa, Hirokazu; Fujimori, Akira; Kato, Takamitsu A; Uesaka, Mitsuru
• Is Part Of: Journal of radiation research. Volume 59:Number 3(2018:May)
• Page Start: 272
• Page End: 281
• Publication Date: 2018-01-24
• Subjects: flavonoid -- aglycone -- monoglucosyl-rutin -- flavonoid composite -- solubilizing effect -- irradiation damage -- radioprotective agent; Radiology, Medical -- Periodicals; Radiobiology -- Periodicals; Radiation -- Periodicals; 616.0757
• DOI: 10.1093/jrr/rrx090
• Languages: English
• ISSNs: 0449-3060

Abstract

Abstract: In this study, three novel flavonoid composite materials, created by combining an aglycone [quercetin (QUE), hesperetin (HES) or naringenin (NAR)] with monoglucosyl rutin (MGR), were designed to test for improved radioprotectivity compared with that provided by administration of MGR alone. Aglycone in the MGR-composite state was highly soluble in water, compared with aglycone alone dissolved in dimethyl sulfoxide or distilled water. The antioxidant activity of the three flavonoid composites was as high as that of MGR only. Next, the cytotoxicity test after 30 min treatment of an MGR composite showed a clear reduction in cell viability and suggested that a rapid introduction of aglycone into cells had taken place. In addition, QUE/MGR and HES/MGR composites strongly scavenged intracellular reactive oxygen species (ROS) induced by X-ray irradiation as well as MGR alone did. However, in the colony-formation assay using irradiated Chinese hamster ovary (CHO) cells, the HES/MGR composite showed a stronger radioprotective effect than MGR alone did, but the QUE/MGR composite showed no additional protective effect compared with the control. Furthermore, it was revealed that QUE and QUE/MGR composite treatment had the effect of reducing the glutathione (GSH) content in cells, and that QUE showed a stronger inhibition of PARP activity compared that of HES and NAR. Our data demonstrated that when designing a flavonoid composite as a radioprotective agent, it was necessary to select an appropriate aglycone, considering not only its antioxidant ability but also its inhibitory effect on cell recovery or DNA repair after radiation injury.