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The present study investigated the effects of polymethoxyflavonoids nobiletin and tangeretin on uridine diphosphate-glucuronosyltransferase (UGT) activity in the livers of dams exposed to 2,3,7,8-tetr...achlorodibenzo-p-dioxin (TCDD). Pregnant Wistar rats received TCDD (1 m g/kg, p.o.) on gestational day (GD) 15, and the hepatic UGT activity and its inducibility using TCDD were assessed at GD20. UGT activity against p-nitrophenol, 4-methylumbelliferone, and SN-38 was significantly induced in hepatic S9 of TCDD-treated rats. Therefore, UGT isoforms involved in the glucuronidation of these substrates are considered TCDD-inducible in pregnant rats. Kinetic analyses were performed for pooled S9 of rats maternally exposed to TCDD and for control rats for SN-38 glucuronidation. Their Km values were comparable, but the Vmax value in TCDD group was greater than that in the control group. Considering the Km value, SN-38 concentration was fixed at 10 m M, and the inhibitory effects of nobiletin and tangeretin were studied. Nobiletin and tangeretin significantly inhibited SN-38 glucuronidation in pooled hepatic S9 in the control rats at 10 m M. Tangeretin also inhibited SN-38 glucuronidation in the TCDD-treated dams at 10 m M, whereas Nobiletin was inclined to inhibit it. At 100 m M, nobiletin and tangeretin inhibited SN-38 glucuronidation in TCDD and control groups. Although their inhibitory properties were similar, tangeretin was slightly stronger than nobiletin. Thus, UGTs are involved in hormone homeostasis. Further analysis is required to determine whether nobiletin and tangeretin reduce the adverse effects of maternal exposure to TCDD via their modulation of TCDD-induced UGT activity.続きを見る
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Mendeley出力
114_1_p065