Design and evaluation of a novel flavonoid-based radioprotective agent utilizing monoglucosyl rutin

Autor: Yasushi Aizawa, Shigeaki Sunada, Mitsuru Uesaka, Hirokazu Hirakawa, Akira Fujimori, Takamitsu A. Kato
Rok vydání: 2018
Předmět:
0301 basic medicine
Naringenin
irradiation damage
Time Factors
Antioxidant
Cell Survival
Rutin
Health
Toxicology and Mutagenesis
medicine.medical_treatment
Flavonoid
Intracellular Space
Radiation-Protective Agents
CHO Cells
Pharmacology
Antioxidants
Colony-Forming Units Assay
03 medical and health sciences
chemistry.chemical_compound
Cricetulus
Picrates
Cricetinae
Regular Paper
aglycone
medicine
Animals
flavonoid
Radiology
Nuclear Medicine and imaging
monoglucosyl-rutin
Flavonoids
chemistry.chemical_classification
Radiation
Dimethyl sulfoxide
Biphenyl Compounds
Hesperetin
Water
Free Radical Scavengers
Glutathione
radioprotective agent
030104 developmental biology
Aglycone
solubilizing effect
Solubility
chemistry
flavonoid composite
Poly(ADP-ribose) Polymerases
Reactive Oxygen Species
Quercetin
Zdroj: Journal of Radiation Research
ISSN: 1349-9157
0449-3060
Popis: 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.
Databáze: OpenAIRE
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