|Budget Amount *help
¥1,500,000 (Direct Cost : ¥1,500,000)
Fiscal Year 1996 : ¥600,000 (Direct Cost : ¥600,000)
Fiscal Year 1995 : ¥900,000 (Direct Cost : ¥900,000)
In order to evaluate chemopreventive activity of flavonoids, the absorption of flavonoids into the circulatory systems of humans and mice, and the protective effects on oxidative stress, were examined in male mice exposed to gamma-ray, ferric nitrilotriacetate (Fe-NTA) and doxorubicin, which generate active oxygen species and induce lipid peroxidation.
HPLC analysis, using Capcell Pak C18-UG 120 column, was carried out to determine the concentrations of eight flavonoids (rutin, myricitrin, quercetin, myricetin, fisetin, kaempferol, luteolin, eriodictyol) in food samples and blood plasma. Lyophilized food samples from seven kinds of meals contained from 5 mg to 30 mg of flavonoids. The concentration of quercetin in human plasma reached the highest level (less than 100ng/ml) 30-60min after ingestion of the meal, which contained 60.8mg of quercetin and 11.4mg of kaempferol. The concentration of quercetin retured to the pro-meal level within 5h. The mouse plasma concentration of alphaG-Rutin reached the highest level 30 min after oral administration and then returned to the control level within 60 min.
When mice received alphaG-Rutin or luteolin by single gastric intubation 30min before gamma irradiation (1.5Gy), a significant reduction in the frequency of micronucleated reticulocytes (MNRETs) was observed. Administration of alphaG-Rutin or luteolin by gastric intubation suppressed lipid peroxidation in the bone marrow, spleen, kidney and heart of gamma-irradiated, Fe-NTA or doxorubicin treated mice. Further, alphaG-Rutin showed a protective effect against subacute nephrotoxicity as revealed by the induction of karyomegalic cells in the renal proximal tubules of mice treated with Fe-NTA.
These results suggest that absorbed flavonoids works as an antioxidant in vivo. Daily intake of flavonoids may contribute to the chemoprevention of free radical-associated diseases such as cancer.